Advertisement

Malignant Mesothelioma

  • Katalin Dobra
  • Anders Hjerpe
Chapter

Abstract

Malignant mesothelioma, the primary tumor of the serosal cavities, is in most cases the fearful consequence of exposure to fibrous minerals such as asbestos and erionite. The diagnosis was previously considered to be a difficult one that required access to biopsy material. The development of ancillary techniques such as immunocytochemistry and fluorescence in situ hybridization has changed this, and guidelines for obtaining a specific diagnosis based on effusion cytology have been recently published. Since the effusion often is the first available diagnostic material, the diagnosis is also obtained earlier in this way, improving patient survival and the chance for therapeutic intervention. The chapter describes the development of the tumor and its molecular background. This is characterized by frequent losses of the suppressor genes NF-2 and BAP-1 and homozygous deletion of p16, while no specific driver mutation has been so far identified. Despite the lack of actionable driver mutations, extensive genome-wide molecular screening combined with chemosensitivity testing of cells derived from pleural effusions has the potential to improve the basis for rational selection of personalized treatment options in the future.

References

  1. 1.
    Wagner JC, Sleggs CA, Marchand P. Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province. Br J Ind Med. 1960;17:260–71.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Wagner JC, Skidmore JW, Hill RJ, Griffiths DM. Erionite exposure and mesotheliomas in rats. Br J Cancer. 1985;51(5):727–30.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Carbone M, Ly BH, Dodson RF, Pagano I, Morris PT, Dogan UA, Gazdar AF, Pass HI, Yang H. Malignant mesothelioma: facts, myths, and hypotheses. J Cell Physiol. 2012;227(1):44–58.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Faig J, Howard S, Levine EA, Casselman G, Hesdorffer M, Ohar JA. Changing pattern in malignant mesothelioma survival. Transl Oncol. 2015;8(1):35–9.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Ai J, Stevenson JP. Current issues in malignant pleural mesothelioma evaluation and management. Oncologist. 2014;19(9):975–84.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Mutsaers SE. Mesothelial cells: their structure, function and role in serosal repair. Respirology. 2002;7(3):171–91.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Mutsaers SE. The mesothelial cell. Int J Biochem Cell Biol. 2004;36(1):9–16.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Mutsaers SE, Kalomenidis I, Wilson NA, Lee YC. Growth factors in pleural fibrosis. Curr Opin Pulm Med. 2006;12(4):251–8.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Mutsaers SE, Di Paolo N. Future directions in mesothelial transplantation research. Int J Artif Organs. 2007;30(6):557–61.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Dobra K, Andang M, Syrokou A, Karamanos NK, Hjerpe A. Differentiation of mesothelioma cells is influenced by the expression of proteoglycans. Exp Cell Res. 2000;258(1):12–22.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Bolen JW, Hammar SP, McNutt MA. Reactive and neoplastic serosal tissue. A light-microscopic, ultrastructural, and immunocytochemical study. Am J Surg Pathol. 1986;10(1):34–47.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Whitaker D, Papadimitriou J. Mesothelial healing: morphological and kinetic investigations. J Pathol. 1985;145(2):159–75.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Foley-Comer AJ, Herrick SE, Al-Mishlab T, Prele CM, Laurent GJ, Mutsaers SE. Evidence for incorporation of free-floating mesothelial cells as a mechanism of serosal healing. J Cell Sci. 2002;115(Pt 7):1383–9.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Warn R, Harvey P, Warn A, Foley-Comer A, Heldin P, Versnel M, Arakaki N, Daikuhara Y, Laurent GJ, Herrick SE, et al. HGF/SF induces mesothelial cell migration and proliferation by autocrine and paracrine pathways. Exp Cell Res. 2001;267(2):258–66.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Herrick SE, Mutsaers SE. Mesothelial progenitor cells and their potential in tissue engineering. Int J Biochem Cell Biol. 2004;36(4):621–42.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Chua F, Dunsmore SE, Clingen PH, Mutsaers SE, Shapiro SD, Segal AW, Roes J, Laurent GJ. Mice lacking neutrophil elastase are resistant to bleomycin-induced pulmonary fibrosis. Am J Pathol. 2007;170(1):65–74.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Herrick SE, Mutsaers SE. The potential of mesothelial cells in tissue engineering and regenerative medicine applications. Int J Artif Organs. 2007;30(6):527–40.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Lansley SM, Searles RG, Hoi A, Thomas C, Moneta H, Herrick SE, Thompson PJ, Newman M, Sterrett GF, Prele CM, et al. Mesothelial cell differentiation into osteoblast- and adipocyte-like cells. J Cell Mol Med. 2011;15(10):2095–105.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Fassina A, Cappellesso R, Guzzardo V, Dalla Via L, Piccolo S, Ventura L, Fassan M. Epithelial-mesenchymal transition in malignant mesothelioma. Mod Pathol. 2012;25(1):86–99.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Klominek J, Robert KH, Hjerpe A, Wickstrom B, Gahrton G. Serum-dependent growth patterns of two, newly established human mesothelioma cell lines. Cancer Res. 1989;49(21):6118–22.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Craighead JE, Mossman BT. The pathogenesis of asbestos-associated diseases. N Engl J Med. 1982;306(24):1446–55.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Sebastien P, Gaudichet A, Bignon J, Baris YI. Zeolite bodies in human lungs from Turkey. Lab Invest. 1981;44(5):420–5.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Carbone M, Emri S, Dogan AU, Steele I, Tuncer M, Pass HI, Baris YI. A mesothelioma epidemic in Cappadocia: scientific developments and unexpected social outcomes. Nat Rev Cancer. 2007;7(2):147–54.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Baumann F, Rougier Y, Ambrosi JP, Robineau BP. Pleural mesothelioma in New Caledonia: an acute environmental concern. Cancer Detect Prev. 2007;31(1):70–6.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Metintas M, Ozdemir N, Hillerdal G, Ucgun I, Metintas S, Baykul C, Elbek O, Mutlu S, Kolsuz M. Environmental asbestos exposure and malignant pleural mesothelioma. Respir Med. 1999;93(5):349–55.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Hillerdal G. Mesothelioma: cases associated with non-occupational and low dose exposures. Occup Environ Med. 1999;56(8):505–13.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Maher B. Epidemiology: fear in the dust. Nature. 2010;468(7326):884–5.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Baris YI, Grandjean P. Prospective study of mesothelioma mortality in Turkish villages with exposure to fibrous zeolite. J Natl Cancer Inst. 2006;98(6):414–7.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    McDonald JC. Epidemiology of malignant mesothelioma—an outline. Ann Occup Hyg. 2010;54(8):851–7.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Lotti M, Bergamo L, Murer B. Occupational toxicology of asbestos-related malignancies. Clin Toxicol (Phila). 2010;48(6):485–96.CrossRefGoogle Scholar
  31. 31.
    Lechner JF, Tokiwa T, LaVeck M, Benedict WF, Banks-Schlegel S, Yeager H Jr, Banerjee A, Harris CC. Asbestos-associated chromosomal changes in human mesothelial cells. Proc Natl Acad Sci U S A. 1985;82(11):3884–8.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Ault JG, Cole RW, Jensen CG, Jensen LC, Bachert LA, Rieder CL. Behavior of crocidolite asbestos during mitosis in living vertebrate lung epithelial cells. Cancer Res. 1995;55(4):792–8.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Hesterberg TW, Barrett JC. Induction by asbestos fibers of anaphase abnormalities: mechanism for aneuploidy induction and possibly carcinogenesis. Carcinogenesis. 1985;6(3):473–5.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Fung H, Kow YW, Van Houten B, Taatjes DJ, Hatahet Z, Janssen YM, Vacek P, Faux SP, Mossman BT. Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells. Cancer Res. 1998;58(2):189–94.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Sekido Y. Molecular pathogenesis of malignant mesothelioma. Carcinogenesis. 2013;34(7):1413–9.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Chew SH, Toyokuni S. Malignant mesothelioma as an oxidative stress-induced cancer: an update. Free Radic Biol Med. 2015;86:166–78.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Francis RJ, Segard T, Morandeau L, Lee YC, Millward MJ, Segal A, Nowak AK. Characterization of hypoxia in malignant pleural mesothelioma with FMISO PET-CT. Lung Cancer. 2015;90(1):55–60.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Bristow RG, Hill RP. Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat Rev Cancer. 2008;8(3):180–92.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Nabavi N, Bennewith KL, Churg A, Wang Y, Collins CC, Mutti L. Switching off malignant mesothelioma: exploiting the hypoxic microenvironment. Genes Cancer. 2016;7(11-12):340–54.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Lechner JF, Tesfaigzi J, Gerwin BI. Oncogenes and tumor-suppressor genes in mesothelioma—a synopsis. Environ Health Perspect. 1997;105(Suppl 5):1061–7.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Lindholm PM, Salmenkivi K, Vauhkonen H, Nicholson AG, Anttila S, Kinnula VL, Knuutila S. Gene copy number analysis in malignant pleural mesothelioma using oligonucleotide array CGH. Cytogenet Genome Res. 2007;119(1-2):46–52.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Musti M, Kettunen E, Dragonieri S, Lindholm P, Cavone D, Serio G, Knuutila S. Cytogenetic and molecular genetic changes in malignant mesothelioma. Cancer Genet Cytogenet. 2006;170(1):9–15.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Gibas Z, Li FP, Antman KH, Bernal S, Stahel R, Sandberg AA. Chromosome changes in malignant mesothelioma. Cancer Genet Cytogenet. 1986;20(3-4):191–201.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Popescu NC, Chahinian AP, DiPaolo JA. Nonrandom chromosome alterations in human malignant mesothelioma. Cancer Res. 1988;48(1):142–7.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Tiainen M, Tammilehto L, Mattson K, Knuutila S. Nonrandom chromosomal abnormalities in malignant pleural mesothelioma. Cancer Genet Cytogenet. 1988;33(2):251–74.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Flejter WL, Li FP, Antman KH, Testa JR. Recurring loss involving chromosomes 1, 3, and 22 in malignant mesothelioma: possible sites of tumor suppressor genes. Genes Chromosomes Cancer. 1989;1(2):148–54.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Hagemeijer A, Versnel MA, Van Drunen E, Moret M, Bouts MJ, van der Kwast TH, Hoogsteden HC. Cytogenetic analysis of malignant mesothelioma. Cancer Genet Cytogenet. 1990;47(1):1–28.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Taguchi T, Jhanwar SC, Siegfried JM, Keller SM, Testa JR. Recurrent deletions of specific chromosomal sites in 1p, 3p, 6q, and 9p in human malignant mesothelioma. Cancer Res. 1993;53(18):4349–55.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Kamb A, Shattuck-Eidens D, Eeles R, Liu Q, Gruis NA, Ding W, Hussey C, Tran T, Miki Y, Weaver-Feldhaus J, et al. Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus. Nat Genet. 1994;8(1):23–6.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Cheng JQ, Jhanwar SC, Klein WM, Bell DW, Lee WC, Altomare DA, Nobori T, Olopade OI, Buckler AJ, Testa JR. p16 alterations and deletion mapping of 9p21-p22 in malignant mesothelioma. Cancer Res. 1994;54(21):5547–51.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Nobori T, Miura K, Wu DJ, Lois A, Takabayashi K, Carson DA. Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature. 1994;368(6473):753–6.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Kratzke RA, Otterson GA, Lincoln CE, Ewing S, Oie H, Geradts J, Kaye FJ. Immunohistochemical analysis of the p16INK4 cyclin-dependent kinase inhibitor in malignant mesothelioma. J Natl Cancer Inst. 1995;87(24):1870–5.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    De Rienzo A, Archer MA, Yeap BY, Dao N, Sciaranghella D, Sideris AC, Zheng Y, Holman AG, Wang YE, Dal Cin PS, et al. Gender-specific molecular and clinical features underlie malignant pleural mesothelioma. Cancer Res. 2016;76(2):319–28.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Illei PB, Ladanyi M, Rusch VW, Zakowski MF. The use of CDKN2A deletion as a diagnostic marker for malignant mesothelioma in body cavity effusions. Cancer. 2003;99(1):51–6.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Ladanyi M. Implications of P16/CDKN2A deletion in pleural mesotheliomas. Lung Cancer. 2005;49(Suppl 1):S95–8.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Savic S, Franco N, Grilli B, Barascud Ade V, Herzog M, Bode B, Loosli H, Spieler P, Schonegg R, Zlobec I, et al. Fluorescence in situ hybridization in the definitive diagnosis of malignant mesothelioma in effusion cytology. Chest. 2010;138(1):137–44.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Lopez-Rios F, Chuai S, Flores R, Shimizu S, Ohno T, Wakahara K, Illei PB, Hussain S, Krug L, Zakowski MF, et al. Global gene expression profiling of pleural mesotheliomas: overexpression of aurora kinases and P16/CDKN2A deletion as prognostic factors and critical evaluation of microarray-based prognostic prediction. Cancer Res. 2006;66(6):2970–9.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, Cox NJ, Dogan AU, Pass HI, Trusa S, et al. Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet. 2011;43(10):1022–5.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Carbone M, Yang H, Pass HI, Krausz T, Testa JR, Gaudino G. BAP1 and cancer. Nat Rev Cancer. 2013;13(3):153–9.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Cheung M, Talarchek J, Schindeler K, Saraiva E, Penney LS, Ludman M, Testa JR. Further evidence for germline BAP1 mutations predisposing to melanoma and malignant mesothelioma. Cancer Genet. 2013;206(5):206–10.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Wang A, Papneja A, Hyrcza M, Al-Habeeb A, Ghazarian D. Gene of the month: BAP1. J Clin Pathol. 2016;69(9):750–3.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Bhattacharya S, Hanpude P, Maiti TK. Cancer associated missense mutations in BAP1 catalytic domain induce amyloidogenic aggregation: a new insight in enzymatic inactivation. Sci Rep. 2015;5:18462.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Dawson A, Gibbs A, Browne K, Pooley F, Griffiths M. Familial mesothelioma. Details of 17 cases with histopathologic findings and mineral analysis. Cancer. 1992;70(5):1183–7.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Attanoos RL, Gibbs AR. Pathology of malignant mesothelioma. Histopathology. 1997;30(5):403–18.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Ascoli V, Aalto Y, Carnovale-Scalzo C, Nardi F, Falzetti D, Mecucci C, Knuutila S. DNA copy number changes in familial malignant mesothelioma. Cancer Genet Cytogenet. 2001;127(1):80–2.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Roushdy-Hammady I, Siegel J, Emri S, Testa JR, Carbone M. Genetic-susceptibility factor and malignant mesothelioma in the Cappadocian region of Turkey. Lancet. 2001;357(9254):444–5.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Pilarski R, Rai K, Cebulla C, Abdel-Rahman M. BAP1 tumor predisposition syndrome. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, et al., editors. GeneReviews(R). Seattle, WA; 1993.Google Scholar
  68. 68.
    Cheung M, Testa JR. BAP1, a tumor suppressor gene driving malignant mesothelioma. Transl Lung Cancer Res. 2017;6(3):270–8.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Nasu M, Emi M, Pastorino S, Tanji M, Powers A, Luk H, Baumann F, Zhang YA, Gazdar A, Kanodia S, et al. High incidence of somatic BAP1 alterations in sporadic malignant mesothelioma. J Thorac Oncol. 2015;10(4):565–76.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Farzin M, Toon CW, Clarkson A, Sioson L, Watson N, Andrici J, Gill AJ. Loss of expression of BAP1 predicts longer survival in mesothelioma. Pathology. 2015;47(4):302–7.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Rai K, Pilarski R, Cebulla CM, Abdel-Rahman MH. Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases. Clin Genet. 2016;89(3):285–94.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Ohar JA, Cheung M, Talarchek J, Howard SE, Howard TD, Hesdorffer M, Peng H, Rauscher FJ, Testa JR. Germline BAP1 mutational landscape of asbestos-exposed malignant mesothelioma patients with family history of cancer. Cancer Res. 2016;76(2):206–15.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Abdel-Rahman MH, Rai K, Pilarski R, Davidorf FH, Cebulla CM. Germline BAP1 mutations misreported as somatic based on tumor-only testing. Fam Cancer. 2016;15(2):327–30.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Betti M, Casalone E, Ferrante D, Aspesi A, Morleo G, Biasi A, Sculco M, Mancuso G, Guarrera S, Righi L et al. Germline mutations in DNA repair genes predispose asbestos-exposed patients to malignant pleural mesothelioma. Cancer Lett. 2017.Google Scholar
  75. 75.
    Cheng JQ, Lee WC, Klein MA, Cheng GZ, Jhanwar SC, Testa JR. Frequent mutations of NF2 and allelic loss from chromosome band 22q12 in malignant mesothelioma: evidence for a two-hit mechanism of NF2 inactivation. Genes Chromosomes Cancer. 1999;24(3):238–42.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Bianchi AB, Mitsunaga SI, Cheng JQ, Klein WM, Jhanwar SC, Seizinger B, Kley N, Klein-Szanto AJ, Testa JR. High frequency of inactivating mutations in the neurofibromatosis type 2 gene (NF2) in primary malignant mesotheliomas. Proc Natl Acad Sci U S A. 1995;92(24):10854–8.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Murakami H, Mizuno T, Taniguchi T, Fujii M, Ishiguro F, Fukui T, Akatsuka S, Horio Y, Hida T, Kondo Y, et al. LATS2 is a tumor suppressor gene of malignant mesothelioma. Cancer Res. 2011;71(3):873–83.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Miyanaga A, Masuda M, Tsuta K, Kawasaki K, Nakamura Y, Sakuma T, Asamura H, Gemma A, Yamada T. Hippo pathway gene mutations in malignant mesothelioma: revealed by RNA and targeted exon sequencing. J Thorac Oncol. 2015;10(5):844–51.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Yokoyama T, Osada H, Murakami H, Tatematsu Y, Taniguchi T, Kondo Y, Yatabe Y, Hasegawa Y, Shimokata K, Horio Y, et al. YAP1 is involved in mesothelioma development and negatively regulated by Merlin through phosphorylation. Carcinogenesis. 2008;29(11):2139–46.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Langerak AW, De Laat PA, Van Der Linden-Van Beurden CA, Delahaye M, Van Der Kwast TH, Hoogsteden HC, Benner R, Versnel MA. Expression of platelet-derived growth factor (PDGF) and PDGF receptors in human malignant mesothelioma in vitro and in vivo. J Pathol. 1996;178(2):151–60.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Langerak AW, van der Linden-van Beurden CA, Versnel MA. Regulation of differential expression of platelet-derived growth factor alpha- and beta-receptor mRNA in normal and malignant human mesothelial cell lines. Biochim Biophys Acta. 1996;1305(1-2):63–70.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Gerwin BI. Cytokine signaling in mesothelial cells: receptor expression closes the autocrine loop. Am J Respir Cell Mol Biol. 1996;14(6):505–7.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Heintz NH, Janssen YM, Mossman BT. Persistent induction of c-fos and c-jun expression by asbestos. Proc Natl Acad Sci U S A. 1993;90(8):3299–303.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Sekido Y. Molecular biology of malignant mesothelioma. Environ Health Prev Med. 2008;13(2):65–70.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Maki-Nevala S, Sarhadi VK, Knuuttila A, Scheinin I, Ellonen P, Lagstrom S, Ronty M, Kettunen E, Husgafvel-Pursiainen K, Wolff H, et al. Driver gene and novel mutations in asbestos-exposed lung adenocarcinoma and malignant mesothelioma detected by exome sequencing. Lung. 2016;194(1):125–35.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Bueno R, De Rienzo A, Dong L, Gordon GJ, Hercus CF, Richards WG, Jensen RV, Anwar A, Maulik G, Chirieac LR, et al. Second generation sequencing of the mesothelioma tumor genome. PLoS One. 2010;5(5):e10612.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Guo G, Chmielecki J, Goparaju C, Heguy A, Dolgalev I, Carbone M, Seepo S, Meyerson M, Pass HI. Whole-exome sequencing reveals frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1 in malignant pleural mesothelioma. Cancer Res. 2015;75(2):264–9.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Kang HC, Kim HK, Lee S, Mendez P, Kim JW, Woodard G, Yoon JH, Jen KY, Fang LT, Jones K, et al. Whole exome and targeted deep sequencing identify genome-wide allelic loss and frequent SETDB1 mutations in malignant pleural mesotheliomas. Oncotarget. 2016;7(7):8321–31.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Sugarbaker DJ, Richards WG, Gordon GJ, Dong L, De Rienzo A, Maulik G, Glickman JN, Chirieac LR, Hartman ML, Taillon BE, et al. Transcriptome sequencing of malignant pleural mesothelioma tumors. Proc Natl Acad Sci U S A. 2008;105(9):3521–6.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Dong L, Jensen RV, De Rienzo A, Gordon GJ, Xu Y, Sugarbaker DJ, Bueno R. Differentially expressed alternatively spliced genes in malignant pleural mesothelioma identified using massively parallel transcriptome sequencing. BMC Med Genet. 2009;10:149.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Bueno R, Stawiski EW, Goldstein LD, Durinck S, De Rienzo A, Modrusan Z, Gnad F, Nguyen TT, Jaiswal BS, Chirieac LR, et al. Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations. Nat Genet. 2016;48(4):407–16.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Hylebos M, Van Camp G, van Meerbeeck JP, Op de Beeck K. The genetic landscape of malignant pleural mesothelioma: results from massively parallel sequencing. J Thorac Oncol. 2016;11(10):1615–26.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Lo Iacono M, Monica V, Righi L, Grosso F, Libener R, Vatrano S, Bironzo P, Novello S, Musmeci L, Volante M, et al. Targeted next-generation sequencing of cancer genes in advanced stage malignant pleural mesothelioma: a retrospective study. J Thorac Oncol. 2015;10(3):492–9.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Joseph NM, Chen YY, Nasr A, Yeh I, Talevich E, Onodera C, Bastian BC, Rabban JT, Garg K, Zaloudek C, et al. Genomic profiling of malignant peritoneal mesothelioma reveals recurrent alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X. Mod Pathol. 2017;30(2):246–54.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Chirac P, Maillet D, Lepretre F, Isaac S, Glehen O, Figeac M, Villeneuve L, Peron J, Gibson F, Galateau-Salle F, et al. Genomic copy number alterations in 33 malignant peritoneal mesothelioma analyzed by comparative genomic hybridization array. Hum Pathol. 2016;55:72–82.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Alakus H, Yost SE, Woo B, French R, Lin GY, Jepsen K, Frazer KA, Lowy AM, Harismendy O. BAP1 mutation is a frequent somatic event in peritoneal malignant mesothelioma. J Transl Med. 2015;13:122.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Singhi AD, Krasinskas AM, Choudry HA, Bartlett DL, Pingpank JF, Zeh HJ, Luvison A, Fuhrer K, Bahary N, Seethala RR, et al. The prognostic significance of BAP1, NF2, and CDKN2A in malignant peritoneal mesothelioma. Mod Pathol. 2016;29(1):14–24.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Panagopoulos I, Gorunova L, Davidson B, Heim S. Novel TNS3-MAP 3K3 and ZFPM2-ELF5 fusion genes identified by RNA sequencing in multicystic mesothelioma with t(7,17)(p12;q23) and t(8,11)(q23;p13). Cancer Lett. 2015;357(2):502–9.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Kato S, Tomson BN, Buys TP, Elkin SK, Carter JL, Kurzrock R. Genomic landscape of malignant mesotheliomas. Mol Cancer Ther. 2016;15(10):2498–507.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Brevet M, Shimizu S, Bott MJ, Shukla N, Zhou Q, Olshen AB, Rusch V, Ladanyi M. Coactivation of receptor tyrosine kinases in malignant mesothelioma as a rationale for combination targeted therapy. J Thorac Oncol. 2011;6(5):864–74.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Sun X, Wei L, Liden J, Hui G, Dahlman-Wright K, Hjerpe A, Dobra K. Molecular characterization of tumour heterogeneity and malignant mesothelioma cell differentiation by gene profiling. J Pathol. 2005;207(1):91–101.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Gordon GJ, Rockwell GN, Jensen RV, Rheinwald JG, Glickman JN, Aronson JP, Pottorf BJ, Nitz MD, Richards WG, Sugarbaker DJ, et al. Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using large-scale transcriptional profiling. Am J Pathol. 2005;166(6):1827–40.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Rihn BH, Mohr S, McDowell SA, Binet S, Loubinoux J, Galateau F, Keith G, Leikauf GD. Differential gene expression in mesothelioma. FEBS Lett. 2000;480(2-3):95–100.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Sun X, Dobra K, Bjornstedt M, Hjerpe A. Upregulation of 9 genes, including that for thioredoxin, during epithelial differentiation of mesothelioma cells. Differentiation. 2000;66(4-5):181–8.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Singhal S, Wiewrodt R, Malden LD, Amin KM, Matzie K, Friedberg J, Kucharczuk JC, Litzky LA, Johnson SW, Kaiser LR, et al. Gene expression profiling of malignant mesothelioma. Clin Cancer Res. 2003;9(8):3080–97.PubMedPubMedCentralGoogle Scholar
  106. 106.
    Roe OD, Anderssen E, Helge E, Pettersen CH, Olsen KS, Sandeck H, Haaverstad R, Lundgren S, Larsson E. Genome-wide profile of pleural mesothelioma versus parietal and visceral pleura: the emerging gene portrait of the mesothelioma phenotype. PLoS One. 2009;4(8):e6554.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Gray SG, Fennell DA, Mutti L, O’Byrne KJ. In arrayed ranks: array technology in the study of mesothelioma. J Thorac Oncol. 2009;4(3):411–25.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Sahab ZJ, Hall MD, Zhang L, Cheema AK, Byers SW. Tumor suppressor RARRES1 regulates DLG2, PP2A, VCP, EB1, and Ankrd26. J Cancer. 2010;1:14–22.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Holmgren A, Bjornstedt M. Thioredoxin and thioredoxin reductase. Methods Enzymol. 1995;252:199–208.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Rubartelli A, Bajetto A, Allavena G, Wollman E, Sitia R. Secretion of thioredoxin by normal and neoplastic cells through a leaderless secretory pathway. J Biol Chem. 1992;267(34):24161–4.PubMedPubMedCentralGoogle Scholar
  111. 111.
    Williams CH Jr. Thioredoxin-thioredoxin reductase—a system that has come of age. Eur J Biochem. 2000;267(20):6101.PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Williams CH, Arscott LD, Muller S, Lennon BW, Ludwig ML, Wang PF, Veine DM, Becker K, Schirmer RH. Thioredoxin reductase two modes of catalysis have evolved. Eur J Biochem. 2000;267(20):6110–7.PubMedCrossRefPubMedCentralGoogle Scholar
  113. 113.
    Hayashi T, Ueno Y, Okamoto T. Oxidoreductive regulation of nuclear factor kappa B. Involvement of a cellular reducing catalyst thioredoxin. J Biol Chem. 1993;268(15):11380–8.PubMedPubMedCentralGoogle Scholar
  114. 114.
    Kumar-Singh S, Weyler J, Martin MJ, Vermeulen PB, Van Marck E. Angiogenic cytokines in mesothelioma: a study of VEGF, FGF-1 and -2, and TGF beta expression. J Pathol. 1999;189(1):72–8.PubMedCrossRefPubMedCentralGoogle Scholar
  115. 115.
    DeLong P, Carroll RG, Henry AC, Tanaka T, Ahmad S, Leibowitz MS, Sterman DH, June CH, Albelda SM, Vonderheide RH. Regulatory T cells and cytokines in malignant pleural effusions secondary to mesothelioma and carcinoma. Cancer Biol Ther. 2005;4(3):342–6.PubMedCrossRefPubMedCentralGoogle Scholar
  116. 116.
    Jagadeeswaran R, Ma PC, Seiwert TY, Jagadeeswaran S, Zumba O, Nallasura V, Ahmed S, Filiberti R, Paganuzzi M, Puntoni R, et al. Functional analysis of c-Met/hepatocyte growth factor pathway in malignant pleural mesothelioma. Cancer Res. 2006;66(1):352–61.PubMedCrossRefPubMedCentralGoogle Scholar
  117. 117.
    Destro A, Ceresoli GL, Falleni M, Zucali PA, Morenghi E, Bianchi P, Pellegrini C, Cordani N, Vaira V, Alloisio M, et al. EGFR overexpression in malignant pleural mesothelioma. An immunohistochemical and molecular study with clinico-pathological correlations. Lung Cancer. 2006;51(2):207–15.PubMedCrossRefPubMedCentralGoogle Scholar
  118. 118.
    Goto Y, Shinjo K, Kondo Y, Shen L, Toyota M, Suzuki H, Gao W, An B, Fujii M, Murakami H, et al. Epigenetic profiles distinguish malignant pleural mesothelioma from lung adenocarcinoma. Cancer Res. 2009;69(23):9073–82.PubMedCrossRefPubMedCentralGoogle Scholar
  119. 119.
    Christensen BC, Houseman EA, Poage GM, Godleski JJ, Bueno R, Sugarbaker DJ, Wiencke JK, Nelson HH, Marsit CJ, Kelsey KT. Integrated profiling reveals a global correlation between epigenetic and genetic alterations in mesothelioma. Cancer Res. 2010;70(14):5686–94.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Kannerstein M, Churg J. Mesothelioma in man and experimental animals. Environ Health Perspect. 1980;34:31–6.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Johansson L, Linden CJ. Aspects of histopathologic subtype as a prognostic factor in 85 pleural mesotheliomas. Chest. 1996;109(1):109–14.PubMedCrossRefPubMedCentralGoogle Scholar
  122. 122.
    Segal A, Sterrett GF, Frost FA, Shilkin KB, Olsen NJ, Musk AW, Nowak AK, Robinson BW, Creaney J. A diagnosis of malignant pleural mesothelioma can be made by effusion cytology: results of a 20 year audit. Pathology. 2013;45(1):44–8.PubMedCrossRefPubMedCentralGoogle Scholar
  123. 123.
    Hjerpe A, Ascoli V, Bedrossian CW, Boon ME, Creaney J, Davidson B, Dejmek A, Dobra K, Fassina A, Field A, et al. Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology. Acta Cytol. 2015;59(1):2–16.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Husain AN, Colby TV, Ordonez NG, Allen TC, Attanoos RL, Beasley MB, Butnor KJ, Chirieac LR, Churg AM, Dacic S et al. Guidelines for pathologic diagnosis of malignant mesothelioma: 2017 update of the Consensus Statement from the International Mesothelioma Interest Group. Arch Pathol Lab Med. 2017.Google Scholar
  125. 125.
    Dejmek A, Hjerpe A. Immunohistochemical reactivity in mesothelioma and adenocarcinoma: a stepwise logistic regression analysis. Apmis. 1994;102(4):255–64.PubMedCrossRefPubMedCentralGoogle Scholar
  126. 126.
    Ordonez NG. Role of immunohistochemistry in differentiating epithelial mesothelioma from adenocarcinoma. Review and update. Am J Clin Pathol. 1999;112(1):75–89.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Brockstedt U, Gulyas M, Dobra K, Dejmek A, Hjerpe A. An optimized battery of eight antibodies that can distinguish most cases of epithelial mesothelioma from adenocarcinoma. Am J Clin Pathol. 2000;114(2):203–9.PubMedCrossRefPubMedCentralGoogle Scholar
  128. 128.
    Carella R, Deleonardi G, D’Errico A, Salerno A, Egarter-Vigl E, Seebacher C, Donazzan G, Grigioni WF. Immunohistochemical panels for differentiating epithelial malignant mesothelioma from lung adenocarcinoma: a study with logistic regression analysis. Am J Surg Pathol. 2001;25(1):43–50.PubMedCrossRefPubMedCentralGoogle Scholar
  129. 129.
    Warhol MJ, Hickey WF, Corson JM. Malignant mesothelioma: ultrastructural distinction from adenocarcinoma. Am J Surg Pathol. 1982;6(4):307–14.PubMedCrossRefPubMedCentralGoogle Scholar
  130. 130.
    Stoebner P, Brambilla E. Ultrastructural diagnosis of pleural tumors. Pathol Res Pract. 1982;173(4):402–16.PubMedCrossRefPubMedCentralGoogle Scholar
  131. 131.
    Nurminen M, Dejmek A, Martensson G, Thylen A, Hjerpe A. Clinical utility of liquid-chromatographic analysis of effusions for hyaluronate content. Clin Chem. 1994;40(5):777–80.PubMedPubMedCentralGoogle Scholar
  132. 132.
    Robinson BW, Creaney J, Lake R, Nowak A, Musk AW, de Klerk N, Winzell P, Hellstrom KE, Hellstrom I. Mesothelin-family proteins and diagnosis of mesothelioma. Lancet. 2003;362(9396):1612–6.PubMedCrossRefPubMedCentralGoogle Scholar
  133. 133.
    Dejmek A, Brockstedt U, Hjerpe A. Optimization of a battery using nine immunocytochemical variables for distinguishing between epithelial mesothelioma and adenocarcinoma. Apmis. 1997;105(11):889–94.PubMedCrossRefPubMedCentralGoogle Scholar
  134. 134.
    Dejmek A, Hjerpe A. The combination of CEA, EMA, and BerEp4 and hyaluronan analysis specifically identifies 79% of all histologically verified mesotheliomas causing an effusion. Diagn Cytopathol. 2005;32(3):160–6.PubMedCrossRefPubMedCentralGoogle Scholar
  135. 135.
    Davidson B. The diagnostic and molecular characteristics of malignant mesothelioma and ovarian/peritoneal serous carcinoma. Cytopathology. 2011;22(1):5–21.PubMedCrossRefPubMedCentralGoogle Scholar
  136. 136.
    Davidson B. New diagnostic and molecular characteristics of malignant mesothelioma. Ultrastruct Pathol. 2008;32(6):227–40.PubMedCrossRefPubMedCentralGoogle Scholar
  137. 137.
    Davidson B, Nielsen S, Christensen J, Asschenfeldt P, Berner A, Risberg B, Johansen P. The role of desmin and N-cadherin in effusion cytology: a comparative study using established markers of mesothelial and epithelial cells. Am J Surg Pathol. 2001;25(11):1405–12.PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Attanoos RL, Griffin A, Gibbs AR. The use of immunohistochemistry in distinguishing reactive from neoplastic mesothelium. A novel use for desmin and comparative evaluation with epithelial membrane antigen, p53, platelet-derived growth factor-receptor, P-glycoprotein and Bcl-2. Histopathology. 2003;43(3):231–8.PubMedCrossRefPubMedCentralGoogle Scholar
  139. 139.
    Parham DM, Webber B, Holt H, Williams WK, Maurer H. Immunohistochemical study of childhood rhabdomyosarcomas and related neoplasms. Results of an Intergroup Rhabdomyosarcoma study project. Cancer. 1991;67(12):3072–80.PubMedCrossRefPubMedCentralGoogle Scholar
  140. 140.
    Sheffield BS, Hwang HC, Lee AF, Thompson K, Rodriguez S, Tse CH, Gown AM, Churg A. BAP1 immunohistochemistry and p16 FISH to separate benign from malignant mesothelial proliferations. Am J Surg Pathol. 2015;39(7):977–82.PubMedCrossRefPubMedCentralGoogle Scholar
  141. 141.
    McGregor SM, Dunning R, Hyjek E, Vigneswaran W, Husain AN, Krausz T. BAP1 facilitates diagnostic objectivity, classification, and prognostication in malignant pleural mesothelioma. Hum Pathol. 2015;46(11):1670–8.PubMedCrossRefPubMedCentralGoogle Scholar
  142. 142.
    Cigognetti M, Lonardi S, Fisogni S, Balzarini P, Pellegrini V, Tironi A, Bercich L, Bugatti M, Rossi G, Murer B, et al. BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations. Mod Pathol. 2015;28(8):1043–57.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Andrici J, Sheen A, Sioson L, Wardell K, Clarkson A, Watson N, Ahadi MS, Farzin M, Toon CW, Gill AJ. Loss of expression of BAP1 is a useful adjunct, which strongly supports the diagnosis of mesothelioma in effusion cytology. Mod Pathol. 2015;28(10):1360–8.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Hwang HC, Sheffield BS, Rodriguez S, Thompson K, Tse CH, Gown AM, Churg A. Utility of BAP1 immunohistochemistry and p16 (CDKN2A) FISH in the diagnosis of malignant mesothelioma in effusion cytology specimens. Am J Surg Pathol. 2016;40(1):120–6.PubMedPubMedCentralCrossRefGoogle Scholar
  145. 145.
    Shen J, Pinkus GS, Deshpande V, Cibas ES. Usefulness of EMA, GLUT-1, and XIAP for the cytologic diagnosis of malignant mesothelioma in body cavity fluids. Am J Clin Pathol. 2009;131(4):516–23.PubMedCrossRefPubMedCentralGoogle Scholar
  146. 146.
    Hasteh F, Lin GY, Weidner N, Michael CW. The use of immunohistochemistry to distinguish reactive mesothelial cells from malignant mesothelioma in cytologic effusions. Cancer Cytopathol. 2010;118(2):90–6.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Minato H, Kurose N, Fukushima M, Nojima T, Usuda K, Sagawa M, Sakuma T, Ooi A, Matsumoto I, Oda M, et al. Comparative immunohistochemical analysis of IMP3, GLUT1, EMA, CD146, and desmin for distinguishing malignant mesothelioma from reactive mesothelial cells. Am J Clin Pathol. 2014;141(1):85–93.PubMedCrossRefPubMedCentralGoogle Scholar
  148. 148.
    Flores-Staino C, Darai-Ramqvist E, Dobra K, Hjerpe A, et al. Lung cancer. 2010;68(1):39–43.PubMedCrossRefPubMedCentralGoogle Scholar
  149. 149.
    Legrand M, Pariente R. Ultrastructural study of pleural fluid in mesothelioma. Thorax. 1974;29(2):164–71.PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Henderson DW, Papadimitriou JM, Coleman M. Ultrastructural appearances of tumours. Edinburgh: Churchill Livingstone; 1986.Google Scholar
  151. 151.
    Ghadially F. Diagnostic electron microscopy of tumours. London: Butterworth; 1985. p. 96–105.CrossRefGoogle Scholar
  152. 152.
    Blix G. Hyaluronic acid in the pleural and peritoneal fluids from a case of mesothelioma. Acta Soc Med Ups. 1951;56(1-2):47–50.PubMedPubMedCentralGoogle Scholar
  153. 153.
    Harington JS, Wagner JC, Smith M. The detection of hyaluronic acid in pleural fluids of cases with diffuse pleural mesotheliomas. Br J Exp Pathol. 1963;44:81–3.PubMedPubMedCentralGoogle Scholar
  154. 154.
    Asplund T, Versnel MA, Laurent TC, Heldin P. Human mesothelioma cells produce factors that stimulate the production of hyaluronan by mesothelial cells and fibroblasts. Cancer Res. 1993;53(2):388–92.PubMedPubMedCentralGoogle Scholar
  155. 155.
    Liu Z, Dobra K, Hauzenberger D, Klominek J. Expression of hyaluronan synthases and hyaluronan in malignant mesothelioma cells. Anticancer Res. 2004;24(2B):599–603.PubMedPubMedCentralGoogle Scholar
  156. 156.
    Hjerpe A. Liquid-chromatographic determination of hyaluronic acid in pleural and ascitic fluids. Clin Chem. 1986;32(6):952–6.PubMedPubMedCentralGoogle Scholar
  157. 157.
    Chichibu K, Matsuura T, Shichijo S, Yokoyama MM. Assay of serum hyaluronic acid in clinical application. Clin Chim Acta. 1989;181(3):317–23.PubMedCrossRefPubMedCentralGoogle Scholar
  158. 158.
    Mundt F, Nilsonne G, Arslan S, Csuros K, Hillerdal G, Yildirim H, Metintas M, Dobra K, Hjerpe A. Hyaluronan and N-ERC/mesothelin as key biomarkers in a specific two-step model to predict pleural malignant mesothelioma. PLoS One. 2013;8(8):e72030.PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Engstrom-Laurent A, Hallgren R. Circulating hyaluronate in rheumatoid arthritis: relationship to inflammatory activity and the effect of corticosteroid therapy. Ann Rheum Dis. 1985;44(2):83–8.PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Engstrom-Laurent A, Loof L, Nyberg A, Schroder T. Increased serum levels of hyaluronate in liver disease. Hepatology. 1985;5(4):638–42.PubMedCrossRefPubMedCentralGoogle Scholar
  161. 161.
    Fraser JR, Laurent TC, Engstrom-Laurent A, Laurent UG. Elimination of hyaluronic acid from the blood stream in the human. Clin Exp Pharmacol Physiol. 1984;11(1):17–25.PubMedCrossRefPubMedCentralGoogle Scholar
  162. 162.
    Thylen A, Wallin J, Martensson G. Hyaluronan in serum as an indicator of progressive disease in hyaluronan-producing malignant mesothelioma. Cancer. 1999;86(10):2000–5.PubMedCrossRefGoogle Scholar
  163. 163.
    Rump A, Morikawa Y, Tanaka M, Minami S, Umesaki N, Takeuchi M, Miyajima A. Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion. J Biol Chem. 2004;279(10):9190–8.PubMedCrossRefPubMedCentralGoogle Scholar
  164. 164.
    Hollevoet K, Bernard D, De Geeter F, Walgraeve N, Van den Eeckhaut A, Vanholder R, Van de Wiele C, Stove V, van Meerbeeck JP, Delanghe JR. Glomerular filtration rate is a confounder for the measurement of soluble mesothelin in serum. Clin Chem. 2009;55(7):1431–3.PubMedCrossRefPubMedCentralGoogle Scholar
  165. 165.
    Creaney J, Olsen NJ, Brims F, Dick IM, Musk AW, de Klerk NH, Skates SJ, Robinson BW. Serum mesothelin for early detection of asbestos-induced cancer malignant mesothelioma. Cancer Epidemiol Biomarkers Prev. 2010;19(9):2238–46.PubMedCrossRefPubMedCentralGoogle Scholar
  166. 166.
    Shiomi K, Miyamoto H, Segawa T, Hagiwara Y, Ota A, Maeda M, Takahashi K, Masuda K, Sakao Y, Hino O. Novel ELISA system for detection of N-ERC/mesothelin in the sera of mesothelioma patients. Cancer Sci. 2006;97(9):928–32.PubMedCrossRefPubMedCentralGoogle Scholar
  167. 167.
    Pass HI, Lott D, Lonardo F, Harbut M, Liu Z, Tang N, Carbone M, Webb C, Wali A. Asbestos exposure, pleural mesothelioma, and serum osteopontin levels. N Engl J Med. 2005;353(15):1564–73.PubMedCrossRefPubMedCentralGoogle Scholar
  168. 168.
    Grigoriu BD, Scherpereel A, Devos P, Chahine B, Letourneux M, Lebailly P, Gregoire M, Porte H, Copin MC, Lassalle P. Utility of osteopontin and serum mesothelin in malignant pleural mesothelioma diagnosis and prognosis assessment. Clin Cancer Res. 2007;13(10):2928–35.PubMedCrossRefPubMedCentralGoogle Scholar
  169. 169.
    Raiko I, Sander I, Weber DG, Raulf-Heimsoth M, Gillissen A, Kollmeier J, Scherpereel A, Bruning T, Johnen G. Development of an enzyme-linked immunosorbent assay for the detection of human calretinin in plasma and serum of mesothelioma patients. BMC Cancer. 2010;10:242.PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Gulyas M, Hjerpe A. Proteoglycans and WT1 as markers for distinguishing adenocarcinoma, epithelioid mesothelioma, and benign mesothelium. J Pathol. 2003;199(4):479–87.PubMedCrossRefPubMedCentralGoogle Scholar
  171. 171.
    Kumar-Singh S, Jacobs W, Dhaene K, Weyn B, Bogers J, Weyler J, Van Marck E. Syndecan-1 expression in malignant mesothelioma: correlation with cell differentiation, WT1 expression, and clinical outcome. J Pathol. 1998;186(3):300–5.PubMedCrossRefPubMedCentralGoogle Scholar
  172. 172.
    Saqi A, Yun SS, Yu GH, Alexis D, Taub RN, Powell CA, Borczuk AC. Utility of CD138 (syndecan-1) in distinguishing carcinomas from mesotheliomas. Diagn Cytopathol. 2005;33(2):65–70.PubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    Seidel C, Gulyas M, David G, Dobra K, Theocharis AD, Hjerpe A. A sandwich ELISA for the estimation of human syndecan-2 and syndecan-4 in biological samples. J Pharm Biomed Anal. 2004;34(4):797–801.PubMedCrossRefPubMedCentralGoogle Scholar
  174. 174.
    Tsuji S, Tsuura Y, Morohoshi T, Shinohara T, Oshita F, Yamada K, Kameda Y, Ohtsu T, Nakamura Y, Miyagi Y. Secretion of intelectin-1 from malignant pleural mesothelioma into pleural effusion. Br J Cancer. 2010;103(4):517–23.PubMedPubMedCentralCrossRefGoogle Scholar
  175. 175.
    Chen Z, Gaudino G, Pass HI, Carbone M, Yang H. Diagnostic and prognostic biomarkers for malignant mesothelioma: an update. Transl Lung Cancer Res. 2017;6(3):259–69.PubMedPubMedCentralCrossRefGoogle Scholar
  176. 176.
    Rundlof AK, Fernandes AP, Selenius M, Babic M, Shariatgorji M, Nilsonne G, Ilag LL, Dobra K, Bjornstedt M. Quantification of alternative mRNA species and identification of thioredoxin reductase 1 isoforms in human tumor cells. Differentiation. 2007;75(2):123–32.PubMedCrossRefPubMedCentralGoogle Scholar
  177. 177.
    Mundt F, Heidari-Hamedani G, Nilsonne G, Metintas M, Hjerpe A, Dobra K. Diagnostic and prognostic value of soluble syndecan-1 in pleural malignancies. Biomed Res Int. 2014;2014:419853.PubMedPubMedCentralCrossRefGoogle Scholar
  178. 178.
    Mundt F, Johansson HJ, Forshed J, Arslan S, Metintas M, Dobra K, Lehtio J, Hjerpe A. Proteome screening of pleural effusions identifies galectin 1 as a diagnostic biomarker and highlights several prognostic biomarkers for malignant mesothelioma. Mol Cell Proteomics. 2014;13(3):701–15.PubMedCrossRefPubMedCentralGoogle Scholar
  179. 179.
    Yuan Y, Nymoen DA, Stavnes HT, Rosnes AK, Bjorang O, Wu C, Nesland JM, Davidson B. Tenascin-X is a novel diagnostic marker of malignant mesothelioma. Am J Surg Pathol. 2009;33(11):1673–82.PubMedPubMedCentralCrossRefGoogle Scholar
  180. 180.
    Aerts JG, Delahaye M, van der Kwast TH, Davidson B, Hoogsteden HC, van Meerbeeck JP. The high post-test probability of a cytological examination renders further investigations to establish a diagnosis of epithelial malignant pleural mesothelioma redundant. Diagn Cytopathol. 2006;34(8):523–7.PubMedCrossRefPubMedCentralGoogle Scholar
  181. 181.
    Cedres S, Ponce-Aix S, Zugazagoitia J, Sansano I, Enguita A, Navarro-Mendivil A, Martinez-Marti A, Martinez P, Felip E. Analysis of expression of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM). PLoS One. 2015;10(3):e0121071.PubMedPubMedCentralCrossRefGoogle Scholar
  182. 182.
    Khanna S, Thomas A, Abate-Daga D, Zhang J, Morrow B, Steinberg SM, Orlandi A, Ferroni P, Schlom J, Guadagni F, et al. Malignant mesothelioma effusions are infiltrated by CD3+ T cells highly expressing PD-L1 and the PD-L1+ tumor cells within these effusions are susceptible to ADCC by the anti-PD-L1 antibody Avelumab. J Thorac Oncol. 2016;11(11):1993–2005.PubMedPubMedCentralCrossRefGoogle Scholar
  183. 183.
    Mansfield AS, Roden AC, Peikert T, Sheinin YM, Harrington SM, Krco CJ, Dong H, Kwon ED. B7-H1 expression in malignant pleural mesothelioma is associated with sarcomatoid histology and poor prognosis. J Thorac Oncol. 2014;9(7):1036–40.PubMedPubMedCentralCrossRefGoogle Scholar
  184. 184.
    Dozier J, Zheng H, Adusumilli PS. Immunotherapy for malignant pleural mesothelioma: current status and future directions. Transl Lung Cancer Res. 2017;6(3):315–24.PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Bakker E, Guazzelli A, Ashtiani F, Demonacos C, Krstic-Demonacos M, Mutti L. Immunotherapy advances for mesothelioma treatment. Expert Rev Anticancer Ther. 2017;17:799–814.PubMedCrossRefPubMedCentralGoogle Scholar
  186. 186.
    Alley EW, Lopez J, Santoro A, Morosky A, Saraf S, Piperdi B, van Brummelen E. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Lancet Oncol. 2017;18(5):623–30.PubMedCrossRefPubMedCentralGoogle Scholar
  187. 187.
    Wu L, de Perrot M. Radio-immunotherapy and chemo-immunotherapy as a novel treatment paradigm in malignant pleural mesothelioma. Transl Lung Cancer Res. 2017;6(3):325–34.PubMedPubMedCentralCrossRefGoogle Scholar
  188. 188.
    Alley EW, Katz SI, Cengel KA, Simone CB II. Immunotherapy and radiation therapy for malignant pleural mesothelioma. Transl Lung Cancer Res. 2017;6(2):212–9.PubMedPubMedCentralCrossRefGoogle Scholar
  189. 189.
    Klug F, Prakash H, Huber PE, Seibel T, Bender N, Halama N, Pfirschke C, Voss RH, Timke C, Umansky L, et al. Low-dose irradiation programs macrophage differentiation to an iNOS(+)/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer Cell. 2013;24(5):589–602.PubMedCrossRefPubMedCentralGoogle Scholar
  190. 190.
    Lizotte PH, Jones RE, Keogh L, Ivanova E, Liu H, Awad MM, Hammerman PS, Gill RR, Richards WG, Barbie DA, et al. Fine needle aspirate flow cytometric phenotyping characterizes immunosuppressive nature of the mesothelioma microenvironment. Sci Rep. 2016;6:31745.PubMedPubMedCentralCrossRefGoogle Scholar
  191. 191.
    Zucali PA, Giovannetti E, Assaraf YG, Ceresoli GL, Peters GJ, Santoro A. New tricks for old biomarkers: thymidylate synthase expression as a predictor of pemetrexed activity in malignant mesothelioma. Ann Oncol. 2010;21(7):1560–1.PubMedCrossRefPubMedCentralGoogle Scholar
  192. 192.
    Uramoto H, Onitsuka T, Shimokawa H, Hanagiri T. TS, DHFR and GARFT expression in non-squamous cell carcinoma of NSCLC and malignant pleural mesothelioma patients treated with pemetrexed. Anticancer Res. 2010;30(10):4309–15.PubMedPubMedCentralGoogle Scholar
  193. 193.
    Vilmar A, Sorensen JB. Excision repair cross-complementation group 1 (ERCC1) in platinum-based treatment of non-small cell lung cancer with special emphasis on carboplatin: a review of current literature. Lung Cancer. 2009;64(2):131–9.PubMedCrossRefPubMedCentralGoogle Scholar
  194. 194.
    Mansour MSI, Seidal T, Mager U, Baigi A, Dobra K, Dejmek A. Determination of PD-L1 expression in effusions from mesothelioma by immuno-cytochemical staining. Cancer Cytopathol. 2017;125(12):908–17.  https://doi.org/10.1002/cncy.21917.CrossRefPubMedPubMedCentralGoogle Scholar
  195. 195.
    Szulkin A, Nilsonne G, Mundt F, Wasik AM, Souri P, Hjerpe A, Dobra K. Variation in drug sensitivity of malignant mesothelioma cell lines with substantial effects of selenite and bortezomib, highlights need for individualized therapy. PLoS One. 2013;8(6):e65903.PubMedPubMedCentralCrossRefGoogle Scholar
  196. 196.
    Markasz L, Kis LL, Stuber G, Flaberg E, Otvos R, Eksborg S, Skribek H, Olah E, Szekely L. Hodgkin-lymphoma-derived cells show high sensitivity to dactinomycin and paclitaxel. Leuk Lymphoma. 2007;48(9):1835–45.PubMedCrossRefPubMedCentralGoogle Scholar
  197. 197.
    Flaberg E, Markasz L, Petranyi G, Stuber G, Dicso F, Alchihabi N, Olah E, Csizy I, Jozsa T, Andren O, et al. High throughput live cell imaging reveals differential inhibition of tumor cell proliferation by human fibroblasts. Int J Cancer. 2011;128(12):2793–802.PubMedCrossRefPubMedCentralGoogle Scholar
  198. 198.
    Szulkin A, Otvos R, Hillerdal CO, Celep A, Yousef-Fadhel E, Skribek H, Hjerpe A, Szekely L, Dobra K. Characterization and drug sensitivity profiling of primary malignant mesothelioma cells from pleural effusions. BMC Cancer. 2014;14:709.PubMedPubMedCentralCrossRefGoogle Scholar
  199. 199.
    Alifrangis C, Janssen JQ, Badhai J, Iorio F, Schunselaar L, Kolluri K, Baas P, Garnett M, McDermott U. High throughput therapeutic screening of malignant pleural mesothelioma (MPM) to identify correlation of sensitivity to FGFR inhibitors with BAP1 inactivation. J Clin Oncol. 2015;33(15).Google Scholar
  200. 200.
    Roe OD, Szulkin A, Anderssen E, Flatberg A, Sandeck H, Amundsen T, Erlandsen SE, Dobra K, Sundstrom SH. Molecular resistance fingerprint of pemetrexed and platinum in a long-term survivor of mesothelioma. PLoS One. 2012;7(8):e40521.PubMedPubMedCentralCrossRefGoogle Scholar
  201. 201.
    Takeuchi S, Seike M, Noro R, Soeno C, Sugano T, Zou F, Uesaka H, Nishijima N, Matsumoto M, Minegishi Y, et al. Significance of osteopontin in the sensitivity of malignant pleural mesothelioma to pemetrexed. Int J Oncol. 2014;44(6):1886–94.PubMedCrossRefPubMedCentralGoogle Scholar
  202. 202.
    Costello JC, Heiser LM, Georgii E, Gonen M, Menden MP, Wang NJ, Bansal M, Ammad-ud-din M, Hintsanen P, Khan SA, et al. A community effort to assess and improve drug sensitivity prediction algorithms. Nat Biotechnol. 2014;32(12):1202–12.PubMedPubMedCentralCrossRefGoogle Scholar
  203. 203.
    Khan SA, Faisal A, Mpindi JP, Parkkinen JA, Kalliokoski T, Poso A, Kallioniemi OP, Wennerberg K, Kaski S. Comprehensive data-driven analysis of the impact of chemoinformatic structure on the genome-wide biological response profiles of cancer cells to 1159 drugs. BMC Bioinform. 2012;13:112.CrossRefGoogle Scholar
  204. 204.
    Jaklitsch MT, Grondin SC, Sugarbaker DJ. Treatment of malignant mesothelioma. World J Surg. 2001;25(2):210–7.PubMedCrossRefPubMedCentralGoogle Scholar
  205. 205.
    Molnar-Kimber KL, Sterman DH, Chang M, Kang EH, ElBash M, Lanuti M, Elshami A, Gelfand K, Wilson JM, Kaiser LR, et al. Impact of preexisting and induced humoral and cellular immune responses in an adenovirus-based gene therapy phase I clinical trial for localized mesothelioma. Hum Gene Ther. 1998;9(14):2121–33.PubMedCrossRefPubMedCentralGoogle Scholar
  206. 206.
    Sterman DH, Treat J, Litzky LA, Amin KM, Coonrod L, Molnar-Kimber K, Recio A, Knox L, Wilson JM, Albelda SM, et al. Adenovirus-mediated herpes simplex virus thymidine kinase/ganciclovir gene therapy in patients with localized malignancy: results of a phase I clinical trial in malignant mesothelioma. Hum Gene Ther. 1998;9(7):1083–92.PubMedCrossRefPubMedCentralGoogle Scholar
  207. 207.
    Caminschi I, Venetsanakos E, Leong CC, Garlepp MJ, Robinson BW, Scott B. Cytokine gene therapy of mesothelioma. Immune and antitumor effects of transfected interleukin-12. Am J Respir Cell Mol Biol. 1999;21(3):347–56.PubMedCrossRefPubMedCentralGoogle Scholar
  208. 208.
    McLaren BR, Whitaker D, Robinson BW, Lake RA. Expression and integrity of DNA topoisomerase II isoforms does not explain generic drug resistance in malignant mesothelioma. Cancer Chemother Pharmacol. 2001;48(1):1–8.PubMedCrossRefPubMedCentralGoogle Scholar
  209. 209.
    Segers K, Kumar-Singh S, Weyler J, Bogers J, Ramael M, Van Meerbeeck J, Van Marck E. Glutathione S-transferase expression in malignant mesothelioma and non-neoplastic mesothelium: an immunohistochemical study. J Cancer Res Clin Oncol. 1996;122(10):619–24.PubMedCrossRefPubMedCentralGoogle Scholar
  210. 210.
    Dejmek A, Brockstedt U, Hjerpe A. Immunoreactivity of pleural malignant mesotheliomas to glutathione S-transferases. Apmis. 1998;106(4):489–94.PubMedCrossRefPubMedCentralGoogle Scholar
  211. 211.
    Soini Y, Kinnula V, Kaarteenaho-Wiik R, Kurttila E, Linnainmaa K, Paakko P. Apoptosis and expression of apoptosis regulating proteins bcl-2, mcl-1, bcl-X, and bax in malignant mesothelioma. Clin Cancer Res. 1999;5(11):3508–15.PubMedPubMedCentralGoogle Scholar
  212. 212.
    Gordon GJ, Appasani K, Parcells JP, Mukhopadhyay NK, Jaklitsch MT, Richards WG, Sugarbaker DJ, Bueno R. Inhibitor of apoptosis protein-1 promotes tumor cell survival in mesothelioma. Carcinogenesis. 2002;23(6):1017–24.PubMedCrossRefPubMedCentralGoogle Scholar
  213. 213.
    Xia C, Xu Z, Yuan X, Uematsu K, You L, Li K, Li L, McCormick F, Jablons DM. Induction of apoptosis in mesothelioma cells by antisurvivin oligonucleotides. Mol Cancer Ther. 2002;1(9):687–94.PubMedPubMedCentralGoogle Scholar
  214. 214.
    Kleinberg L, Lie AK, Florenes VA, Nesland JM, Davidson B. Expression of inhibitor-of-apoptosis protein family members in malignant mesothelioma. Hum Pathol. 2007;38(7):986–94.PubMedCrossRefPubMedCentralGoogle Scholar
  215. 215.
    Zaffaroni N, Costa A, Pennati M, De Marco C, Affini E, Madeo M, Erdas R, Cabras A, Kusamura S, Baratti D, et al. Survivin is highly expressed and promotes cell survival in malignant peritoneal mesothelioma. Cell Oncol. 2007;29(6):453–66.PubMedPubMedCentralGoogle Scholar
  216. 216.
    Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21(14):2636–44.PubMedCrossRefPubMedCentralGoogle Scholar
  217. 217.
    Hillerdal G, Sorensen JB, Sundstrom S, Vikstrom A, Hjerpe A. Treatment of malignant pleural mesothelioma with liposomized doxorubicine: prolonged time to progression and good survival. A Nordic study. Clin Respir J. 2008;2(2):80–5.PubMedCrossRefPubMedCentralGoogle Scholar
  218. 218.
    Schunselaar LM, Quispel-Janssen JM, Neefjes JJ, Baas P. A catalogue of treatment and technologies for malignant pleural mesothelioma. Expert Rev Anticancer Ther. 2016;16(4):455–63.PubMedCrossRefPubMedCentralGoogle Scholar
  219. 219.
    Remon J, Reguart N, Corral J, Lianes P. Malignant pleural mesothelioma: new hope in the horizon with novel therapeutic strategies. Cancer Treat Rev. 2015;41(1):27–34.PubMedCrossRefPubMedCentralGoogle Scholar
  220. 220.
    Signorelli D, Macerelli M, Proto C, Vitali M, Cona MS, Agustoni F, Zilembo N, Platania M, Trama A, Gallucci R, et al. Systemic approach to malignant pleural mesothelioma: what news of chemotherapy, targeted agents and immunotherapy? Tumori. 2016;102(1):18–30.PubMedCrossRefPubMedCentralGoogle Scholar
  221. 221.
    Guazzelli A, Bakker E, Tian K, Demonacos C, Krstic-Demonacos M, Mutti L. Promising investigational drug candidates in phase I and phase II clinical trials for mesothelioma. Expert Opin Investig Drugs. 2017;26(8):933–44.PubMedCrossRefPubMedCentralGoogle Scholar
  222. 222.
    Christoph DC, Eberhardt WE. Systemic treatment of malignant pleural mesothelioma: new agents in clinical trials raise hope of relevant improvements. Curr Opin Oncol. 2014;26(2):171–81.PubMedCrossRefPubMedCentralGoogle Scholar
  223. 223.
    Papa S, Popat S, Shah R, Prevost AT, Lal R, McLennan B, Cane P, Lang-Lazdunski L, Viney Z, Dunn JT, et al. Phase 2 study of sorafenib in malignant mesothelioma previously treated with platinum-containing chemotherapy. J Thorac Oncol. 2013;8(6):783–7.PubMedCrossRefPubMedCentralGoogle Scholar
  224. 224.
    Zimling ZG, Sorensen JB, Gerds TA, Bech C, Andersen CB, Santoni-Rugiu E. A biomarker profile for predicting efficacy of cisplatin-vinorelbine therapy in malignant pleural mesothelioma. Cancer Chemother Pharmacol. 2012;70(5):743–54.PubMedCrossRefPubMedCentralGoogle Scholar
  225. 225.
    Ting S, Mairinger FD, Hager T, Welter S, Eberhardt WE, Wohlschlaeger J, Schmid KW, Christoph DC. ERCC1, MLH1, MSH2, MSH6, and betaIII-tubulin: resistance proteins associated with response and outcome to platinum-based chemotherapy in malignant pleural mesothelioma. Clin Lung Cancer. 2013;14(5):558–67. e553PubMedCrossRefPubMedCentralGoogle Scholar
  226. 226.
    Palumbo C, Bei R, Procopio A, Modesti A. Molecular targets and targeted therapies for malignant mesothelioma. Curr Med Chem. 2008;15(9):855–67.PubMedCrossRefPubMedCentralGoogle Scholar
  227. 227.
    Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D, Molinier O, Corre R, Monnet I, Gounant V, et al. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet. 2016;387(10026):1405–14.PubMedCrossRefPubMedCentralGoogle Scholar
  228. 228.
    Suzuki K, Kadota K, Sima CS, Sadelain M, Rusch VW, Travis WD, Adusumilli PS. Chronic inflammation in tumor stroma is an independent predictor of prolonged survival in epithelioid malignant pleural mesothelioma patients. Cancer Immunol Immunother. 2011;60(12):1721–8.PubMedCrossRefPubMedCentralGoogle Scholar
  229. 229.
    Campbell NP, Kindler HL. Update on malignant pleural mesothelioma. Semin Respir Crit Care Med. 2011;32(1):102–10.PubMedCrossRefPubMedCentralGoogle Scholar
  230. 230.
    Bongiovanni M, Cassoni P, De Giuli P, Viberti L, Cappia S, Ivaldi C, Chiusa L, Bussolati G. p27(kip1) immunoreactivity correlates with long-term survival in pleural malignant mesothelioma. Cancer. 2001;92(5):1245–50.PubMedCrossRefPubMedCentralGoogle Scholar
  231. 231.
    Cedres S, Montero MA, Zamora E, Martinez A, Martinez P, Farinas L, Navarro A, Torrejon D, Gabaldon A, Ramon YCS, et al. Expression of Wilms’ tumor gene (WT1) is associated with survival in malignant pleural mesothelioma. Clin Transl Oncol. 2014;16(9):776–82.PubMedCrossRefPubMedCentralGoogle Scholar
  232. 232.
    Kao SC, Klebe S, Henderson DW, Reid G, Chatfield M, Armstrong NJ, Yan TD, Vardy J, Clarke S, van Zandwijk N, et al. Low calretinin expression and high neutrophil-to-lymphocyte ratio are poor prognostic factors in patients with malignant mesothelioma undergoing extrapleural pneumonectomy. J Thorac Oncol. 2011;6(11):1923–9.PubMedCrossRefPubMedCentralGoogle Scholar
  233. 233.
    Thylen A, Hjerpe A, Martensson G. Hyaluronan content in pleural fluid as a prognostic factor in patients with malignant pleural mesothelioma. Cancer. 2001;92(5):1224–30.PubMedCrossRefPubMedCentralGoogle Scholar
  234. 234.
    Creaney J, Dick IM, Segal A, Musk AW, Robinson BW. Pleural effusion hyaluronic acid as a prognostic marker in pleural malignant mesothelioma. Lung Cancer. 2013;82(3):491–8.PubMedCrossRefPubMedCentralGoogle Scholar
  235. 235.
    Edwards JG, Swinson DE, Jones JL, Waller DA, O’Byrne KJ. EGFR expression: associations with outcome and clinicopathological variables in malignant pleural mesothelioma. Lung Cancer. 2006;54(3):399–407.PubMedCrossRefPubMedCentralGoogle Scholar
  236. 236.
    Levallet G, Vaisse-Lesteven M, Le Stang N, Ilg AG, Brochard P, Astoul P, Pairon JC, Bergot E, Zalcman G, Galateau-Salle F. Plasma cell membrane localization of c-MET predicts longer survival in patients with malignant mesothelioma: a series of 157 cases from the MESOPATH Group. J Thorac Oncol. 2012;7(3):599–606.PubMedCrossRefPubMedCentralGoogle Scholar
  237. 237.
    Amatya VJ, Takeshima Y, Aoe K, Fujimoto N, Okamoto T, Yamada T, Kishimoto T, Morimoto C, Inai K. CD9 expression as a favorable prognostic marker for patients with malignant mesothelioma. Oncol Rep. 2013;29(1):21–8.PubMedCrossRefPubMedCentralGoogle Scholar
  238. 238.
    Aoe K, Amatya VJ, Fujimoto N, Ohnuma K, Hosono O, Hiraki A, Fujii M, Yamada T, Dang NH, Takeshima Y, et al. CD26 overexpression is associated with prolonged survival and enhanced chemosensitivity in malignant pleural mesothelioma. Clin Cancer Res. 2012;18(5):1447–56.PubMedCrossRefPubMedCentralGoogle Scholar
  239. 239.
    Otterstrom C, Soltermann A, Opitz I, Felley-Bosco E, Weder W, Stahel RA, Triponez F, Robert JH, Serre-Beinier V. CD74: a new prognostic factor for patients with malignant pleural mesothelioma. Br J Cancer. 2014;110(8):2040–6.PubMedPubMedCentralCrossRefGoogle Scholar
  240. 240.
    Schramm A, Opitz I, Thies S, Seifert B, Moch H, Weder W, Soltermann A. Prognostic significance of epithelial-mesenchymal transition in malignant pleural mesothelioma. Eur J Cardiothorac Surg. 2010;37(3):566–72.PubMedCrossRefPubMedCentralGoogle Scholar
  241. 241.
    Cristaudo A, Foddis R, Vivaldi A, Guglielmi G, Dipalma N, Filiberti R, Neri M, Ceppi M, Paganuzzi M, Ivaldi GP, et al. Clinical significance of serum mesothelin in patients with mesothelioma and lung cancer. Clin Cancer Res. 2007;13(17):5076–81.PubMedCrossRefPubMedCentralGoogle Scholar
  242. 242.
    Schneider J, Hoffmann H, Dienemann H, Herth FJ, Meister M, Muley T. Diagnostic and prognostic value of soluble mesothelin-related proteins in patients with malignant pleural mesothelioma in comparison with benign asbestosis and lung cancer. J Thorac Oncol. 2008;3(11):1317–24.PubMedCrossRefPubMedCentralGoogle Scholar
  243. 243.
    Cappia S, Righi L, Mirabelli D, Ceppi P, Bacillo E, Ardissone F, Molinaro L, Scagliotti GV, Papotti M. Prognostic role of osteopontin expression in malignant pleural mesothelioma. Am J Clin Pathol. 2008;130(1):58–64.PubMedCrossRefPubMedCentralGoogle Scholar
  244. 244.
    Hollevoet K, Nackaerts K, Gosselin R, De Wever W, Bosquee L, De Vuyst P, Germonpre P, Kellen E, Legrand C, Kishi Y, et al. Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma. J Thorac Oncol. 2011;6(11):1930–7.PubMedCrossRefPubMedCentralGoogle Scholar
  245. 245.
    Creaney J, Dick IM, Meniawy TM, Leong SL, Leon JS, Demelker Y, Segal A, Musk AW, Lee YC, Skates SJ, et al. Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma. Thorax. 2014;69(10):895–902.PubMedPubMedCentralCrossRefGoogle Scholar
  246. 246.
    Righi L, Cavallo MC, Gatti G, Monica V, Rapa I, Busso S, Albera C, Volante M, Scagliotti GV, Papotti M. Tumor/stromal caveolin-1 expression patterns in pleural mesothelioma define a subgroup of the epithelial histotype with poorer prognosis. Am J Clin Pathol. 2014;141(6):816–27.PubMedCrossRefPubMedCentralGoogle Scholar
  247. 247.
    Edwards JG, Cox G, Andi A, Jones JL, Walker RA, Waller DA, O’Byrne KJ. Angiogenesis is an independent prognostic factor in malignant mesothelioma. Br J Cancer. 2001;85(6):863–8.PubMedPubMedCentralCrossRefGoogle Scholar
  248. 248.
    Kao SC, Harvie R, Paturi F, Taylor R, Davey R, Abraham R, Clarke S, Marx G, Cullen M, Kerestes Z, et al. The predictive role of serum VEGF in an advanced malignant mesothelioma patient cohort treated with thalidomide alone or combined with cisplatin/gemcitabine. Lung Cancer. 2012;75(2):248–54.PubMedCrossRefPubMedCentralGoogle Scholar
  249. 249.
    Tabata C, Hirayama N, Tabata R, Yasumitsu A, Yamada S, Murakami A, Iida S, Tamura K, Fukuoka K, Kuribayashi K, et al. A novel clinical role for angiopoietin-1 in malignant pleural mesothelioma. Eur Respir J. 2010;36(5):1099–105.PubMedCrossRefPubMedCentralGoogle Scholar
  250. 250.
    Righi L, Papotti MG, Ceppi P, Bille A, Bacillo E, Molinaro L, Ruffini E, Scagliotti GV, Selvaggi G. Thymidylate synthase but not excision repair cross-complementation group 1 tumor expression predicts outcome in patients with malignant pleural mesothelioma treated with pemetrexed-based chemotherapy. J Clin Oncol. 2010;28(9):1534–9.PubMedCrossRefPubMedCentralGoogle Scholar
  251. 251.
    Zucali PA, Giovannetti E, Destro A, Mencoboni M, Ceresoli GL, Gianoncelli L, Lorenzi E, De Vincenzo F, Simonelli M, Perrino M, et al. Thymidylate synthase and excision repair cross-complementing group-1 as predictors of responsiveness in mesothelioma patients treated with pemetrexed/carboplatin. Clin Cancer Res. 2011;17(8):2581–90.PubMedCrossRefPubMedCentralGoogle Scholar
  252. 252.
    Christoph DC, Asuncion BR, Mascaux C, Tran C, Lu X, Wynes MW, Gauler TC, Wohlschlaeger J, Theegarten D, Neumann V, et al. Folylpoly-glutamate synthetase expression is associated with tumor response and outcome from pemetrexed-based chemotherapy in malignant pleural mesothelioma. J Thorac Oncol. 2012;7(9):1440–8.PubMedPubMedCentralCrossRefGoogle Scholar
  253. 253.
    Davidson B. Prognostic factors in malignant pleural mesothelioma. Hum Pathol. 2015;46(6):789–804.PubMedCrossRefPubMedCentralGoogle Scholar
  254. 254.
    Achatzy R, Beba W, Ritschler R, Worn H, Wahlers B, Macha HN, Morgan JA. The diagnosis, therapy and prognosis of diffuse malignant mesothelioma. Eur J Cardiothorac Surg. 1989;3(5):445–447; discussion 448.PubMedCrossRefPubMedCentralGoogle Scholar
  255. 255.
    Law MR, Gregor A, Hodson ME, Bloom HJ, Turner-Warwick M. Malignant mesothelioma of the pleura: a study of 52 treated and 64 untreated patients. Thorax. 1984;39(4):255–9.PubMedPubMedCentralCrossRefGoogle Scholar
  256. 256.
    Blayney JK, Ceresoli GL, Castagneto B, O’Brien ME, Hasan B, Sylvester R, Rudd R, Steele J, Busacca S, Porta C, et al. Response to chemotherapy is predictive in relation to longer overall survival in an individual patient combined-analysis with pleural mesothelioma. Eur J Cancer. 2012;48(16):2983–92.PubMedCrossRefPubMedCentralGoogle Scholar
  257. 257.
    Own SA, Hillerdal G, Dobra K, Hjerpe A. PP01.05: Early diagnosis by cytology improves survival. In: 13th International Conference of the International Mesothelioma Group, 2016, Birmingham.Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Pathology, Department of Laboratory MedicineKarolinska InstituteStockholmSweden

Personalised recommendations