Peritoneal Mesothelioma: Disease Biology and Patterns of Peritoneal Dissemination



Mesothelioma is a rare neoplasm arising from the mesothelial cells lining the pleura, peritoneum, pericardium, and tunica vaginalis layer of testis [1]. Diffuse malignant peritoneal mesothelioma (DMPM) represents about one-fifth to one-third of all forms of mesothelioma.


  1. 1.
    Robinson BWS, Lake RA. Advanced in malignant mesothelioma. N Engl J Med. 2005;353:1591–603.PubMedGoogle Scholar
  2. 2.
    Conti S, Minelli G, Ascoli V, Marinaccio A, Bonafede M, Manno V, Crialesi R, Straif K. Peritoneal mesothelioma in Italy: trends and geography of mortality and incidence. Am J Ind Med. 2015;58:1050–8.PubMedGoogle Scholar
  3. 3.
    Boffetta P. Epidemiology of peritoneal mesothelioma: a review. Ann Oncol. 2007;18:985–90.PubMedGoogle Scholar
  4. 4.
    Sugarbaker PH, Welch LS, Mohamed F, Glehen O. A review of peritoneal mesothelioma at the Washington Cancer Institute. Surg Oncol Clin N Am. 2003;12:605–21.PubMedGoogle Scholar
  5. 5.
    Gazdar AF, Carbone M. Molecular pathogenesis of mesothelioma and its relationship to Simian virus 40. Clin Lung Cancer. 2003;5:177–81.PubMedGoogle Scholar
  6. 6.
    Roushdy-Hammady I, Siegel J, Emri S, et al. Genetic-susceptibility factor and malignant mesothelioma in the Cappadocian region of Turkey. Lancet. 2001;357:444–5.PubMedGoogle Scholar
  7. 7.
    Churg A, Roggli VL, Galateau-Salle F, et al. Tumours of the pleura: mesothelial tumours. In: Travis WD, Brambilla E, Harris CC, Muller-Hermelink HK, editors. Pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARC Press; 2004.Google Scholar
  8. 8.
    Husain AN, Colby TV, Ordóñez NG, 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. 2018;142:89–108.PubMedGoogle Scholar
  9. 9.
    Battifora H, McCaughey WTE. Tumours and pseudotumours of the serosal membranes. In: Atlas of tumour pathology 3rd series, fascicle 15. Washington, DC: Armed Forces Institute of Pathology; 1995. p. 15–88.Google Scholar
  10. 10.
    Roggli VL, Cagle PT. Pleura, pericardium and peritoneum. In: Silverberg SG, DeLellis RA, Frable WJ, LiVolsi VA, Wick MR, editors. Silverberg’s principles and practice of surgical pathology. 4th ed. New York: Churchill-Livingstone/Elsevier; 2006. p. 1005–39.Google Scholar
  11. 11.
    Allen TC, Cagle PT, Churg AM, Colby TV, Gibbs AR, Hammar SP, Corson JM, Grimes MM, Ordonez NG, Roggli V, Travis WD, Wick MR. Localized malignant mesothelioma. Am J Surg Pathol. 2005;29:7.Google Scholar
  12. 12.
    Baratti D, Kusamura S, Cabras AD, Laterza B, Balestra MR, Deraco M. Lymph node metastases in diffuse malignant peritoneal mesothelioma. Ann Surg Oncol. 2010;17:45–53.PubMedGoogle Scholar
  13. 13.
    Butnor KJ, Sporn TA, Hammar SP, Roggli VL. Well-differentiated papillary mesothelioma. Am J Surg Pathol. 2001;25:1304–9.PubMedGoogle Scholar
  14. 14.
    Baratti D, Kusamura S, Nonaka D, Oliva GD, Laterza B, Deraco M. Multicystic and well-differentiated papillary peritoneal mesothelioma treated by surgical cytoreduction and hyperthermic intra-peritoneal chemotherapy (HIPEC). Ann Surg Oncol. 2007;14:2790–7.PubMedGoogle Scholar
  15. 15.
    de Pangher V, Recchia L, Cafferata M, et al. Malignant peritoneal mesothelioma: a multicenter study on 81 cases. Ann Oncol. 2010;21:348–53.Google Scholar
  16. 16.
    Park JY, Kim KW, Kwon HJ, et al. Peritoneal mesotheliomas: clinicopathologic features, CT findings, and differential diagnosis. Am J Roentgenol. 2008;191:814–25.Google Scholar
  17. 17.
    Whitley N, Brenner D, Antman K, Grant D, Aisner J. CT of peritoneal mesothelioma: analysis of eight cases. Am J Roentgenol. 1982;138:531–5.Google Scholar
  18. 18.
    Yan TD, Haveric N, Carmignani CP, Chang D, Sugarbaker PH. Abdominal computed tomography scans in the selection of patients with malignant peritoneal mesothelioma for comprehensive treatment with cytoreductive surgery and perioperative intraperitoneal chemotherapy. Cancer. 2005;103:839–49.PubMedGoogle Scholar
  19. 19.
    Baratti D, Kusamura S, Martinetti A, Seregni E, Oliva DG, Laterza B, Deraco M. Circulating CA125 in patients with peritoneal mesothelioma treated with cytoreductive surgery and intraperitoneal hyperthermic perfusion. Ann Surg Oncol. 2007;14:500–8.PubMedGoogle Scholar
  20. 20.
    Bruno F, Baratti D, Martinetti A, Morelli D, Sottotetti E, Bonini C, Guaglio M, Kusamura S, Deraco M. Mesothelin and osteopontin as circulating markers of diffuse malignant peritoneal mesothelioma: a preliminary study. Eur J Surg Oncol. 2018;44:792–8.PubMedGoogle Scholar
  21. 21.
    Laterza B, Kusamura S, Baratti D, Oliva GD, Deraco M. Role of explorative laparoscopy to evaluate optimal candidates for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal mesothelioma. In Vivo. 2009;23:187–90.PubMedGoogle Scholar
  22. 22.
    Churg A, Colby TV, Cagle P. The separation of benign and malignant mesothelial proliferations. Am J Surg Pathol. 2000;24:1183–200.PubMedGoogle Scholar
  23. 23.
    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;43:231–8.PubMedGoogle Scholar
  24. 24.
    Ordonez NG. Immunohistochemical diagnosis of epithelioid mesothelioma: an update. Arch Pathol Lab Med. 2005;129:1407–14.PubMedGoogle Scholar
  25. 25.
    Rogoff EE, Hilaris B, Huvos AG. Long-term survival in patients with malignant peritoneal mesothelioma treated with irradiation. Cancer. 1973;32:656–64.PubMedGoogle Scholar
  26. 26.
    Chahinian AP, Pajak TF, Holland JF, et al. Diffuse malignant mesothelioma. Prospective evaluation of 69 patients. Ann Intern Med. 1982;96:746–55.PubMedGoogle Scholar
  27. 27.
    Antman KH, Osteen R, Klegar K, et al. Early peritoneal mesothelioma: a treatable malignancy. Lancet. 1985;2:977–81.PubMedGoogle Scholar
  28. 28.
    Kirmani S, Cleary SM, Mowry J, et al. Intracavitary cisplatin for malignant mesothelioma: an update. Proc Am Clin Oncol. 1988;7. (Abstract 1057).Google Scholar
  29. 29.
    van Gelder T, Hoogsteden HC, Versnel MA, et al. Malignant peritoneal mesothelioma: a series of 19 cases. Digestion. 1989;43:222–7.PubMedGoogle Scholar
  30. 30.
    Markman M, Kelsen D. Efficacy of cisplatin-based intraperitoneal chemotherapy as treatment of malignant peritoneal mesothelioma. J Cancer Res Clin Oncol. 1992;118:547–50.PubMedGoogle Scholar
  31. 31.
    Neumann V, Muller KM, Fischer M. Peritoneal mesothelioma-incidence and aetiology. Pathologe. 1999;20:169–76.PubMedGoogle Scholar
  32. 32.
    Eltabbakh GH, Piver MS, Hempling RE, et al. Clinical picture, response to therapy, and survival of women with diffuse malignant peritoneal mesothelioma. J Surg Oncol. 1999;70:6–12.PubMedGoogle Scholar
  33. 33.
    Sugarbaker PH. Peritonectomy procedures. Ann Surg. 1995;221:29–42.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Baratti D, Kusamura S, Cabras AD, Deraco M. Cytoreductive surgery with selective versus complete parietal peritonectomy followed by hyperthermic intraperitoneal chemotherapy in patients with diffuse malignant peritoneal mesothelioma: a controlled study. Ann Surg Oncol. 2012;19:1416–24.PubMedGoogle Scholar
  35. 35.
    Deraco M, Baratti D, Kusamura S, Laterza B, Balestra MR. Surgical technique of parietal and visceral peritonectomy for peritoneal surface malignancies. J Surg Oncol. 2009;100:321–8.PubMedGoogle Scholar
  36. 36.
    Jaquet P, Sugarbaker PH. Current methodologies for clinical assessment of patients with peritoneal carcinomatosis. J Exp Clin Cancer Res. 1996;15:49–58.Google Scholar
  37. 37.
    Blackham AU, Shen P, Stewart JH, et al. Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for malignant peritoneal mesothelioma: mitomycin versus cisplatin. Ann Surg Oncol. 2010;17:1720–7.Google Scholar
  38. 38.
    Feldman AL, Libutti SK, Pingpank JF, et al. Analysis of factors associated with outcome in patients with malignant peritoneal mesothelioma undergoing surgical debulking and intraperitoneal chemotherapy. J Clin Oncol. 2003;21:4560–7.PubMedGoogle Scholar
  39. 39.
    Robella M, Vaira M, Mellano A, et al. Treatment of diffuse malignant peritoneal mesothelioma (DMPM) by cytoreductive surgery and HIPEC. Minerva Chir. 2014;69:9–15.PubMedGoogle Scholar
  40. 40.
    Borczuk AC, Taub RN, Hesdorffer M, et al. P16 loss and mitotic activity predict poor survival in patients with peritoneal malignant mesothelioma. Clin Cancer Res. 2005;11:3303–8.PubMedGoogle Scholar
  41. 41.
    Cerruto CA, Brun EA, Chang D, Sugarbaker PH. Prognostic significance of histomorphologic parameters in diffuse malignant peritoneal mesothelioma. Arch Pathol Lab Med. 2006;130:1654–61.PubMedGoogle Scholar
  42. 42.
    Elias D, Bedard V, Bouzid T, et al. Malignant peritoneal mesothelioma: treatment with maximal cytoreductive surgery plus intraperitoneal chemotherapy. Gastroenterol Clin Biol. 2007;31:784–8.PubMedGoogle Scholar
  43. 43.
    Chua TC, Yan TD, Morris DL. Outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma: the Australian experience. J Surg Oncol. 2009;99:109–13.PubMedGoogle Scholar
  44. 44.
    Gilani SNS, Mehta A, Garcia-Fadrique A, et al. Outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma and predictors of survival. Int J Hyperthermia. 2018;34:578–84.PubMedGoogle Scholar
  45. 45.
    Baratti D, Kusamura S, Cabras AD, Bertulli R, Hutanu I, Deraco M. Diffuse malignant peritoneal mesothelioma: long-term survival with complete cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Eur J Cancer. 2013;49:3140–8.PubMedGoogle Scholar
  46. 46.
    Yan TD, Deraco M, Baratti D, et al. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma—a multi-institutional registry study. J Clin Oncol. 2009;27:6237–42.PubMedGoogle Scholar
  47. 47.
    Alexander HR Jr, Bartlett DL, Pingpank JF, et al. Treatment factors associated with long-term survival after cytoreductive surgery and regional chemotherapy for patients with malignant peritoneal mesothelioma. Surgery. 2013;153:779–86.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Hommell-Fontaine J, Isaac S, Passot G, et al. Malignant peritoneal mesothelioma treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: is GLUT1 expression a major prognostic factor? A preliminary study. Ann Surg Oncol. 2013;20:3892–8.PubMedGoogle Scholar
  49. 49.
    Magge D, Zenati MS, Austin F, et al. Malignant peritoneal mesothelioma: prognostic factors and oncologic outcome analysis. Ann Surg Oncol. 2014;21:1159–65.PubMedGoogle Scholar
  50. 50.
    Ihemelandu C, Bijelic L, Sugarbaker PH. Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent or progressive diffuse malignant peritoneal mesothelioma: clinicopathologic characteristics and survival outcome. Ann Surg Oncol. 2015;22:1680–5.PubMedGoogle Scholar
  51. 51.
    Malgras B, Gayat E, Aoun O, et al. Impact of combination chemotherapy in peritoneal mesothelioma Hyperthermic Intraperitoneal chemotherapy (HIPEC): the RENAPE study. Ann Surg Oncol. 2018;25:3271–9.PubMedGoogle Scholar
  52. 52.
    Carteni G, Manegold C, Garcia GM, et al. Malignant peritoneal mesothelioma—results from the international expanded access program using pemetrexed alone or in combination with a platinum agent. Lung Cancer. 2009;64:211–8.PubMedGoogle Scholar
  53. 53.
    Jänne PA, Wozniak AJ, Belani CP, et al. Open-label study of pemetrexed alone or in combination with cisplatin for the treatment of patients with peritoneal mesothelioma: outcomes of an expanded access program. Clin Lung Cancer. 2005;7:40–6.PubMedGoogle Scholar
  54. 54.
    Simon GR, Verschraegen CF, Jänne PA, Langer CJ, Dowlati A, Gadgeel SM, et al. Pemetrexed plus gemcitabine as first-line chemotherapy for patients with peritoneal mesothelioma: final report of a phase II trial. J Clin Oncol. 2008;26:3567–72.PubMedGoogle Scholar
  55. 55.
    Deraco M, Baratti D, Hutanu I, Bertuli R, Kusamura S. The role of perioperative systemic chemotherapy in diffuse malignant peritoneal mesothelioma patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2013;20:1093–100.PubMedGoogle Scholar
  56. 56.
    Kepenekian V, Elias D, Passot G, et al. Diffuse malignant peritoneal mesothelioma: evaluation of systemic chemotherapy with comprehensive treatment through the RENAPE database: multi-institutional retrospective study. Eur J Cancer. 2016;65:69–79.PubMedGoogle Scholar
  57. 57.
    Yan TD, Deraco M, Elias D, Glehen O, Levine EA, Moran BJ, Morris DL, Chua TC, Piso P, Sugarbaker PH, Peritoneal Surface Oncology Group. A novel tumor-node-metastasis (TNM) staging system of diffuse malignant peritoneal mesothelioma using outcome analysis of a multi-institutional database. Cancer. 2011;117:1855–63.PubMedGoogle Scholar
  58. 58.
    Schaub NP, Alimchandani M, Quezado M, et al. A novel nomogram for peritoneal mesothelioma predicts survival. Ann Surg Oncol. 2013;20:555–61.PubMedGoogle Scholar
  59. 59.
    Cao C, Yan TD, Deraco M, Elias D, Glehen O, Levine EA, Moran BJ, Morris DL, Chua TC, Piso P, Sugarbaker PH, Peritoneal Surface Malignancy Group. Importance of gender in diffuse malignant peritoneal mesothelioma. Ann Oncol. 2012;23:1494–8.PubMedGoogle Scholar
  60. 60.
    Votanopoulos KI, Sugarbaker P, Deraco M, et al. Is cytoreductive surgery with hyperthermic intraperitoneal chemotherapy justified for biphasic variants of peritoneal mesothelioma? Outcomes from the peritoneal surface oncology group international registry. Ann Surg Oncol. 2018;25:667–73.PubMedGoogle Scholar
  61. 61.
    Valmary-Degano S, Colpart P, Villeneuve L, et al. Immunohistochemical evaluation of two antibodies against PD-L1 and prognostic significance of PD-L1 expression in epithelioid peritoneal malignant mesothelioma: a RENAPE study. Eur J Surg Oncol. 2017;43:1915–23.PubMedGoogle Scholar
  62. 62.
    Villa R, Daidone MG, Motta R, Venturini L, De Marco C, Vannelli A, Kusamura S, Baratti D, Deraco M, Costa A, Reddel RR, Zaffaroni N. Multiple mechanisms of telomere maintenance exist and differentially affect clinical outcome in diffuse malignant peritoneal mesothelioma. Clin Cancer Res. 2008;14:4134–40.PubMedGoogle Scholar
  63. 63.
    Huang Y, Alzahrani NA, Liauw W, Morris DL. Effects of sex hormones on survival of peritoneal mesothelioma. World J Surg Oncol. 2015;13:210.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Pillai K, Pourgholami MH, Chua TC, Morris DL. Ki67-BCL2 index in prognosis of malignant peritoneal mesothelioma. Am J Cancer Res. 2013;3:411–23.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Pillai K, Pourgholami MH, Chua TC, Morris DL. MUC1 has prognostic significance in malignant peritoneal mesothelioma. Int J Biol Markers. 2013;28:303–12.PubMedGoogle Scholar
  66. 66.
    Singhi AD, Krasinskas AM, Choudry HA, et al. The prognostic significance of BAP1, NF2, and CDKN2A in malignant peritoneal mesothelioma. Mod Pathol. 2016;29:14–24.PubMedGoogle Scholar
  67. 67.
    Krasinskas AM, Borczuk AC, Hartman DJ, et al. Prognostic significance of morphological growth patterns and mitotic index of epithelioid malignant peritoneal mesothelioma. Histopathology. 2016;68:729–37.PubMedGoogle Scholar
  68. 68.
    Li YC, Khashab T, Terhune J, et al. Preoperative thrombocytosis predicts shortened survival in patients with malignant peritoneal mesothelioma undergoing operative Cytoreduction and Hyperthermic Intraperitoneal chemotherapy. Ann Surg Oncol. 2017;24:2259–65.PubMedGoogle Scholar
  69. 69.
    Kusamura S, Torres Mesa PA, Cabras A, Baratti D, Deraco M. The role of Ki-67 and pre-cytoreduction parameters in selecting diffuse malignant peritoneal mesothelioma (DMPM) patients for Cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). Ann Surg Oncol. 2016;23:1468–73.PubMedGoogle Scholar
  70. 70.
    Zaffaroni N, Costa A, Pennati M, De Marco C, Affini E, Madeo M, Erdas R, Cabras A, Kusamura S, Baratti D, Deraco M, Daidone MG. Survivin is highly expressed and promotes cell survival in malignant peritoneal mesothelioma. Cell Oncol. 2007;29:453–66.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Carbone A, Pennati M, Parrino B, et al. Novel 1H-pyrrolo[2,3-b]pyridine derivative nortopsentin analogues: synthesis and antitumor activity in peritoneal mesothelioma experimental models. J Med Chem. 2013;56:7060–72.PubMedGoogle Scholar
  72. 72.
    De Cesare M, Cominetti D, Doldi V, Lopergolo A, Deraco M, Gandellini P, Friedlander S, Landesman Y, Kauffman MG, Shacham S, Pennati M, Zaffaroni N. Anti-tumor activity of selective inhibitors of XPO1/CRM1-mediated nuclear export in diffuse malignant peritoneal mesothelioma: the role of survivin. Oncotarget. 2015;6:13119–32.PubMedPubMedCentralGoogle Scholar
  73. 73.
    Perrone F, Jocollè G, Pennati M. Receptor tyrosine kinase and downstream signalling analysis in diffuse malignant peritoneal mesothelioma. Eur J Cancer. 2010;46:2837–48.PubMedGoogle Scholar
  74. 74.
    Varghese S, Chen Z, Bartlett DL, et al. Activation of the phosphoinositide-3-kinase and mammalian target of rapamycin signaling pathways are associated with shortened survival in patients with malignant peritoneal mesothelioma. Cancer. 2011;117:361–71.PubMedGoogle Scholar
  75. 75.
    Bozzi F, Brich S, Dagrada GP, Negri T, Conca E, Cortelazzi B, Belfiore A, Perrone F, Gualeni AV, Gloghini A, Cabras A, Brenca M, Maestro R, Zaffaroni N, Casali P, Bertulli R, Deraco M, Pilotti S. Epithelioid peritoneal mesothelioma: a hybrid phenotype within a mesenchymal-epithelial/epithelial-mesenchymal transition framework. Oncotarget. 2016;7:75503–17.PubMedPubMedCentralGoogle Scholar
  76. 76.
    Govindan R, Kratzke RA, Herndon JE 2nd, et al., Cancer and Leukemia Group B (CALGB 30101). Gefitinib in patients with malignant mesothelioma: a phase II study by the Cancer and Leukemia Group B Clin Cancer Res. 2005;11:2300–4.Google Scholar
  77. 77.
    Garland LL, Rankin C, Gandara DR, et al. Phase II study of erlotinib in patients with malignant pleural mesothelioma: a Southwest Oncology Group Study. J Clin Oncol. 2007;25:2406–13.PubMedGoogle Scholar
  78. 78.
    Dolly SO, Migali C, Tunariu N, et al. Indolent peritoneal mesothelioma: PI3K-mTOR inhibitors as a novel therapeutic strategy. ESMO Open. 2017;e000101:2.Google Scholar
  79. 79.
    Alakus H, Yost SE, Woo B, et al. BAP1 mutation is a frequent somatic event in peritoneal malignant mesothelioma. J Transl Med. 2015;13:122.PubMedPubMedCentralGoogle Scholar
  80. 80.
    Joseph NM, Chen YY, Nasr A, et al. Genomic profiling of malignant peritoneal mesothelioma reveals recurrent alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X. Mod Pathol. 2017;30:246–54.PubMedGoogle Scholar
  81. 81.
    Chirac P, Maillet D, Lepretre F, et al. Genomic copy alterations in 33 malignant peritoneal mesothelioma analyzed by comparative genomic hybridization array. Hum Pathol. 2016;55:72–82.PubMedGoogle Scholar
  82. 82.
    Leblay N, Leprêtre F, Le Stang N, et al. BAP1 is altered by copy number loss, mutation, and/or loss of protein expression in more than 70% of malignant peritoneal mesotheliomas. J Thorac Oncol. 2017;12:724–33.PubMedGoogle Scholar
  83. 83.
    Cigognetti M, Lonardi S, Fisogni S, et al. BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations. Mod Pathol. 2015;28:1043–57.PubMedGoogle Scholar
  84. 84.
    Andrici J, Sheen A, Sioson L, et al. Loss of expression of BAP1 is a useful adjunct, which strongly supports the diagnosis of mesothelioma in effusion cytology. Mod Pathol. 2015;28:1360–8.PubMedPubMedCentralGoogle Scholar
  85. 85.
    Shrestha R, Nabavi N, Lin YY, et al. BAP1 haploinsufficiency predicts a distinct immunogenic class of malignant peritoneal mesothelioma. Genome Med. 2019;11:8.PubMedPubMedCentralGoogle Scholar
  86. 86.
    Sacco JJ, Kenyani J, Butt Z, et al. Loss of the deubiquitylase BAP1 alters class I histone deacetylase expression and sensitivity of mesothelioma cells to HDAC inhibitors. Oncotarget. 2015;6:13757–71.PubMedPubMedCentralGoogle Scholar
  87. 87.
    LaFave LM, Béguelin W, Koche R, et al. Loss of BAP1 function leads to EZH2-dependent transformation. Nat Med. 2015;21:1344–9.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Calabrò L, Morra A, Giannarelli D, et al. Tremelimumab combined with durvalumab in patients with mesothelioma (NIBIT-MESO-1): an open-label, non-randomised, phase 2 study. Lancet Respir Med. 2018;6:451–60.PubMedGoogle Scholar
  89. 89.
    Khanna S, Thomas A, Abate-Daga D, Zhang J, 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;11:1993–2005.PubMedPubMedCentralGoogle Scholar
  90. 90.
    Chapel DB, Stewart R, Furtado LV, Husain AN, Krausz T, Deftereos G. Tumor PD-L1 expression in malignant pleural and peritoneal mesothelioma by Dako PD-L1 22C3 pharmDx and Dako PD-L1 28-8 pharmDx assays. Hum Pathol. 2019;87:11–7.PubMedGoogle Scholar
  91. 91.
    Hung YP, Dong F, Watkins JC, et al. Identification of alk rearrangements in malignant peritoneal mesothelioma. JAMA Oncol. 2018;4:235–8.PubMedGoogle Scholar
  92. 92.
    Bueno R, Stawiski EW, Goldstein LD, et al. Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations. Nat Genet. 2016;48:407–16.PubMedGoogle Scholar
  93. 93.
    Sciarrillo R, Wojtuszkiewicz A, El Hassouni B, et al. Splicing modulation as novel therapeutic strategy against diffuse malignant peritoneal mesothelioma. EBioMedicine. 2019;39:215–25.PubMedGoogle Scholar
  94. 94.
    Birnie KA, Prêle CM, Thompson PJ, Badrian B, Mutsaers SE. Targeting microRNA to improve diagnostic and therapeutic approaches for malignant mesothelioma. Oncotarget. 2017;8:78193–207.PubMedPubMedCentralGoogle Scholar
  95. 95.
    El Bezawy R, De Cesare M, Pennati M, Deraco M, Gandellini P, Zuco V, Zaffaroni N. Antitumor activity of miR-34a in peritoneal mesothelioma relies on c-MET and AXL inhibition: persistent activation of ERK and AKT signaling as a possible cytoprotective mechanism. J Hematol Oncol. 2017;10:19.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Peritoneal Surface Malignancy Unit, Department of SurgeryFondazione IRCCS, Istituto Nazionale dei TumoriMilanItaly
  2. 2.Molecular Pharmacology Unit, Department of Applied Research and Technological DevelopmentFondazione IRCCS, Istituto Nazionale dei TumoriMilanItaly
  3. 3.Department of PathologyFondazione IRCCS, Istituto Nazionale dei TumoriMilanItaly

Personalised recommendations