Skip to main content
SpringerLink
Log in

Biomarkers in the Management of Peritoneal Metastases

  • Chapter
  • First Online:
Pathology of Peritoneal Metastases

Abstract

Selected patients with peritoneal metastases are treated with a curative intent, the backbone of which is cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC). Despite this aggressive and morbid treatment, a large majority of the patients develop recurrence and/or progressive disease. In the era of molecular oncology, molecular markers have been gaining increasing focus as they not only have prognostic value and can improve patient selection, but can also serve as therapeutic targets for developing systemic therapies. Whole genome sequencing has accelerated the process of biomarker discovery. As the field of peritoneal oncology is evolving, many studies have been done and are ongoing, to assess the utility of biomarkers in various aspects of management of peritoneal metastases. This chapter provides a review of the known and emerging biomarkers related to some common peritoneal tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 129.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Glehen O, Gilly FN, Boutitie F, et al. Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with peri-operative intraperitoneal chemotherapy: a multi-institutional study of 1,290 patients. Cancer. 2010;116(24):5608–18.

    PubMed  Google Scholar 

  2. Saxena A, Valle SJ, Liauw W, Morris DL. Recurrence and survival outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for small bowel adenocarcinoma. Anticancer Res. 2017;37(10):5737–42.

    PubMed  Google Scholar 

  3. Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996;82:359–74.

    CAS  PubMed  Google Scholar 

  4. Karunasena E, Sham J, McMahon KW, Ahuja N. Genomics of peritoneal malignancies. Surg Oncol Clin N Am. 2018;27(3):463–75. https://doi.org/10.1016/j.soc.2018.02.004.

    Article  PubMed  Google Scholar 

  5. Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010;5(6):463–6. https://doi.org/10.1097/COH.0b013e32833ed177.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Puntmann VO. How-to guide on biomarkers: biomarker definitions, validation and applications with examples from cardiovascular disease. Postgrad Med J. 2009;85:538–45.

    CAS  PubMed  Google Scholar 

  7. Henry NL, Hayes DF. Cancer biomarkers. Mol Oncol. 2012;6(2):140–6. https://doi.org/10.1016/j.molonc.2012.01.010. Epub 6 Feb 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Goossens N, Nakagawa S, Sun X, Hoshida Y. Cancer biomarker discovery and validation. Transl Cancer Res. 2015;4(3):256–69. https://doi.org/10.3978/j.issn.2218-676X.2015.06.04.

    Article  CAS  PubMed  Google Scholar 

  9. Chen VW, Ruiz B, Killeen JL, et al. Pathology and classification of ovarian tumors. Cancer. 2003;97:2631–42.

    PubMed  Google Scholar 

  10. Dinulescu DM, Ince TA, Quade BJ, et al. Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med. 2005;11:63–70.

    CAS  PubMed  Google Scholar 

  11. Kindelberger DW, Lee Y, Miron A, et al. Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship. Am J Surg Pathol. 2007;31:161–9.

    PubMed  Google Scholar 

  12. Arjmand M, Zahedi AF. Clinical biomarkers for detection of ovarian cancer. J Mol Cancer. 2019;2(1):3–7.

    Google Scholar 

  13. Ashworth A, Balkwill F, Bast RC, et al. Opportunities and challenges in ovarian cancer research, a perspective from the 11th ovarian cancer action/HHMT Forum, Lake Como, March 2007. Gynecol Oncol. 2008;108(3):652–7.

    PubMed  Google Scholar 

  14. Yang WL, Lu Z, Bast RC Jr. The role of biomarkers in the management of epithelial ovarian cancer. Expert Rev Mol Diagn. 2017;17(6):577–91. https://doi.org/10.1080/14737159.2017.1326820.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Aletti GD, Dowdy SC, Podratz KC, Cliby WA. Relationship among surgical complexity, short-term morbidity, and overall survival in primary surgery for advanced ovarian cancer. Am J Obstet Gynecol. 2007;197(6):676.e1–7.

    Google Scholar 

  16. Van Driel WJ, Koole SN, Sikorska K, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer. N Engl J Med. 2018;378(3):230–40.

    PubMed  Google Scholar 

  17. Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379(26):2495–2505. https://doi.org/10.1056/NEJMoa1810858. Epub 2018 Oct 21.

  18. Espey DK, Wu XC, Swan J, et al. Annual report to the nation on the status of cancer, 1975–2004, featuring cancer in American Indians and Alaska Natives. Cancer. 2007;110(10):2119–52.

    PubMed  Google Scholar 

  19. O’Brien TJ, Beard JB, Underwood LJ, et al. The CA 125 gene: an extracellular superstructure dominated by repeat sequences. Tumour Biol. 2001;22:348–66.

    PubMed  Google Scholar 

  20. Kabawat SE, Bast RC, Welch WR, et al. Immunopathologic characterization of a monoclonal antibody that recognizes common surface antigens of human ovarian tumors of serous, endometrioid, and clear cell types. AJCP. 1983;79:98–104.

    CAS  PubMed  Google Scholar 

  21. Romero I, Bast RC Jr. Minireview: human ovarian cancer: biology, current management, and paths to personalizing therapy. Endocrinology. 2012;153(4):1593–602.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Skates SJ, Jacobs IJ, Knapp RC. Tumor markers in screening for ovarian cancer. Methods Mol Med. 2001;39:61–73.

    CAS  PubMed  Google Scholar 

  23. Skates SJ, Mai P, Horick NK, et al. Large prospective study of ovarian cancer screening in high-risk women: CA125 cut-point defined by menopausal status. Cancer Prev Res (Phila). 2011;4:1401–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Moore RG, Miller MC, Eklund EE, et al. Serum levels of the ovarian cancer biomarker HE4 are decreased in pregnancy and increase with age. AJOG. 2012;206:349.e1–7.

    CAS  Google Scholar 

  25. Montagnana M, Danese E, Giudici S, et al. HE4 in ovarian cancer: from discovery to clinical application. Adv Clin Chem. 2011;55:1–20.

    CAS  PubMed  Google Scholar 

  26. Hassan R, Ho M. Mesothelin targeted cancer immunotherapy. Eur J Cancer. 2008;44:46–53.

    CAS  PubMed  Google Scholar 

  27. McIntosh MW, Drescher C, Karlan B, et al. Combining CA 125 and SMR serum markers for diagnosis and early detection of ovarian carcinoma. Gynecol Oncol. 2004;95:9–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Badgwell D, Lu Z, Cole L, et al. Urinary mesothelin provides greater sensitivity for early stage ovarian cancer than serum mesothelin, urinary hCG free beta subunit and urinary hCG beta core fragment. Gynecol Oncol. 2007;106:490–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Diamandis EP, Scorilas A, Fracchioli S, et al. Human kallikrein 6 (hK6): a new potential serum biomarker for diagnosis and prognosis of ovarian carcinoma. J Clin Oncol. 2003;21:1035–43.

    CAS  PubMed  Google Scholar 

  30. El Sherbini MA, Sallam MM, Shaban EA, et al. Diagnostic value of serum kallikrein-related peptidases 6 and 10 versus CA125 in ovarian cancer. Int J Gynecol Cancer. 2011;21:625–32.

    PubMed  Google Scholar 

  31. Bao LH, Sakaguchi H, Fujimoto J, et al. Osteopontin in metastatic lesions as a prognostic marker in ovarian cancers. J Biomed Sci. 2007;14:373–81.

    CAS  PubMed  Google Scholar 

  32. Nakae M, Iwamoto I, Fujino T, et al. Preoperative plasma osteopontin level as a biomarker complementary to carbohydrate antigen 125 in predicting ovarian cancer. J Obstet Gynaecol Res. 2006;32:309–14.

    CAS  PubMed  Google Scholar 

  33. Gadomska H, Grzechocinska B, Janecki J, et al. Serum lipids concentration in women with benign and malignant ovarian tumours. Eur J Obstet Gynecol Reprod Biol. 2005;120:87–90.

    CAS  PubMed  Google Scholar 

  34. Moore RG, Brown AK, Miller MC, et al. The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol. 2008;108(2):402–8.

    CAS  PubMed  Google Scholar 

  35. Bast RC Jr, Skates S, Lokshin A, Moore RG. Differential diagnosis of a pelvic mass: improved algorithms and novel biomarkers. Int J Gynecol Cancer. 2012;22(Suppl 1):S5–8.

    PubMed  PubMed Central  Google Scholar 

  36. Moore RG, Miller MC, Disilvestro P, et al. Evaluation of the diagnostic accuracy of the risk of ovarian malignancy algorithm in women with a pelvic mass. Obstet Gynecol. 2011;118(2 Pt 1):280–8.

    PubMed  PubMed Central  Google Scholar 

  37. Bandiera E, Romani C, Specchia C, et al. Serum human epididymis protein 4 and risk for ovarian malignancy algorithm as new diagnostic and prognostic tools for epithelial ovarian cancer management. Cancer Epidemiol Biomarkers Prev. 2011;20(12):2496–506.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Molina R, Escudero JM, Auge JM, et al. HE4 a novel tumour marker for ovarian cancer: comparison with CA 125 and ROMA algorithm in patients with gynaecological diseases. Tumour Biol. 2011;32(6):1087–95.

    CAS  PubMed  Google Scholar 

  39. Ruggeri G, Bandiera E, Zanotti L, et al. HE4 and epithelial ovarian cancer: comparison and clinical evaluation of two immunoassays and a combination algorithm. Clin Chim Acta. 2011;412(15–16):1447–53.

    CAS  PubMed  Google Scholar 

  40. Jacob F, Meier M, Caduff R, et al. No benefit from combining HE4 and CA125 as ovarian tumor markers in a clinical setting. Gynecol Oncol. 2011;121(3):487–91.

    CAS  PubMed  Google Scholar 

  41. Montagnana M, Danese E, Ruzzenente O, et al. The ROMA (Risk of Ovarian Malignancy Algorithm) for estimating the risk of epithelial ovarian cancer in women presenting with pelvic mass: is it really useful? Clin Chem Lab Med. 2011;49(3):521–5.

    CAS  PubMed  Google Scholar 

  42. Van Gorp T, Cadron I, Despierre E, et al. HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm. Br J Cancer. 2011;104(5):863–70.

    PubMed  PubMed Central  Google Scholar 

  43. Zhang Z, Chan DW. The road from discovery to clinical diagnostics: lessons learned from the first FDA-cleared in vitro diagnostic multivariate index assay of proteomic biomarkers. Cancer Epidemiol Biomarkers Prev. 2010;19(12):2995–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Ueland FR, Desimone CP, Seamon LG, et al. Effectiveness of a multivariate index assay in the preoperative assessment of ovarian tumors. Obstet Gynecol. 2011;117(6):1289–97.

    PubMed  Google Scholar 

  45. Dudas SP, Chatterjee M, Tainsky MA. Usage of cancer associated autoantibodies in the detection of disease. Cancer Biomarkers. 2010;6(5–6):257–70.

    PubMed  Google Scholar 

  46. Yang W-L, Simmons A, Lu Z, et al. Abstract 2838: TP53 autoantibody can detect CA125 screen negative ovarian cancer cases and can be elevated prior to CA125 in preclinical ovarian cancer. Cancer Res. 2015;75(15 Suppl):2838.

    Google Scholar 

  47. Prahm KP, Novotny GW, Hogdall C, Hogdall E. Current status on microRNAs as biomarkers for ovarian cancer. APMIS. 2016;124(5):337–55.

    PubMed  Google Scholar 

  48. Nakamura K, Sawada K, Yoshimura A, Kinose Y, Nakatsuka E, Kimura T. Clinical relevance of circulating cell-free microRNAs in ovarian cancer. Mol Cancer. 2016;15(1):48.

    PubMed  PubMed Central  Google Scholar 

  49. Pal MK, Jaiswar SP, Dwivedi VN, Tripathi AK, Dwivedi A, Sankhwar P. MicroRNA: a new and promising potential biomarker for diagnosis and prognosis of ovarian cancer. Cancer Biol Med. 2015;12(4):328–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Bettegowda C, Sausen M, Leary RJ, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224):224ra24.

    PubMed  PubMed Central  Google Scholar 

  51. Pereira E, Camacho-Vanegas O, Anand S, et al. Personalized circulating tumor DNA biomarkers dynamically predict treatment response and survival in gynecologic cancers. PLoS One. 2015;10(12):e0145754.

    PubMed  PubMed Central  Google Scholar 

  52. An T, Qin S, Xu Y, et al. Exosomes serve as tumour markers for personalized diagnostics owing to their important role in cancer metastasis. J Extracell Vesicles. 2015;4:27522.

    PubMed  Google Scholar 

  53. Pitteri S, Hanash S. A systems approach to the proteomic identification of novel cancer biomarkers. Dis Markers. 2010;28(4):233–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Hanash S, Taguchi A. Application of proteomics to cancer early detection. Cancer J. 2011;17(6):423–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Huang J, Hu W, Sood AK. Prognostic biomarkers in ovarian cancer. Cancer Biomarkers. 2010;8(4–5):231–51. https://doi.org/10.3233/CBM-2011-0212.

    Article  CAS  PubMed  Google Scholar 

  56. Makar AP, Kristensen GB, Kaern J, Bormer OP, Abeler VM, Trope CG. Prognostic value of pre- and postoperative serum CA 125 levels in ovarian cancer: new aspects and multivariate analysis. Obstet Gynecol. 1992;79:1002–10.

    CAS  PubMed  Google Scholar 

  57. Abdel-Azeez HA, Labib HA, Sharaf SM, Refai AN. HE4 and mesothelin: novel biomarkers of ovarian carcinoma in patients with pelvic masses. Asian Pac J Cancer Prev. 2010;11:111–6.

    PubMed  Google Scholar 

  58. Chambers SK, Kacinski BM, Ivins CM, Carcangiu ML. Overexpression of epithelial macrophage colony-stimulating factor (CSF-1) and CSF-1 receptor: a poor prognostic factor in epithelial ovarian cancer, contrasted with a protective effect of stromal CSF-1. Clin Cancer Res. 1997;3:999–1007.

    CAS  PubMed  Google Scholar 

  59. Matsuzaki H, Kobayashi H, Yagyu T, et al. Plasma bikunin as a favorable prognostic factor in ovarian cancer. J Clin Oncol. 2005;23:1463–72.

    CAS  PubMed  Google Scholar 

  60. Laframboise S, Chapman W, McLaughlin J. Andrulis IL. p53 mutations in epithelial ovarian cancers: possible role in predicting chemoresistance. Cancer J. 2000;6:302–8.

    CAS  PubMed  Google Scholar 

  61. Rudlowski C, Pickart AK, Fuhljahn C, et al. Prognostic significance of vascular endothelial growth factor expression in ovarian cancer patients: a long-term follow-up. Int J Gynecol Cancer. 2006;16(Suppl 1):183–9.

    PubMed  Google Scholar 

  62. Landen CN, Kinch MS, Sood AK. EphA2 as a target for ovarian cancer therapy. Expert Opin Ther Targets. 2005;9:1179–87.

    CAS  PubMed  Google Scholar 

  63. Kleinberg L, Holth A, Trope CG, Reich R, Davidson B. Claudin upregulation in ovarian carcinoma effusions is associated with poor survival. Hum Pathol. 2008;39:747–57.

    CAS  PubMed  Google Scholar 

  64. Lin CK, Chao TK, Yu CP, Yu MH, Jin JS. The expression of six biomarkers in the four most common ovarian cancers: correlation with clinicopathological parameters. APMIS. 2009;117:162–75.

    CAS  PubMed  Google Scholar 

  65. Rubin SC, Finstad CL, Wong GY, Almadrones L, Plante M, Lloyd KO. Prognostic significance of HER-2/neu expression in advanced epithelial ovarian cancer: a multivariate analysis. Am J Obstet Gynecol. 1993;168:162–9.

    CAS  PubMed  Google Scholar 

  66. Akhmedkhanov A, Lundin E, Guller S, et al. Circulating soluble Fas levels and risk of ovarian cancer. BMC Cancer. 2003;3:33. https://doi.org/10.1186/1471-2407-3-33. Published 22 Dec 2003.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Nayak SB, Bhat VR, Upadhyay D, Udupa SL. Copper and ceruloplasmin status in serum of prostate and colon cancer patients. Indian J Physiol Pharmacol. 2003;47:108–10.

    CAS  PubMed  Google Scholar 

  68. Kluger HM, Kluger Y, Gilmore-Hebert M, DiVito K, Chang JT, et al. cDNA microarray analysis of invasive and tumorigenic phenotypes in a breast cancer model. Lab Invest. 2004;84:320–31.

    CAS  PubMed  Google Scholar 

  69. Lee CM, Lo HW, Shao RP, Wang SC, Xia W, Gershenson DM, Hung MC. Selective activation of ceruloplasmin promoter in ovarian tumors: potential use for gene therapy. Cancer Res. 2004;64:1788–93.

    CAS  PubMed  Google Scholar 

  70. Huang H, Li Y, Liu J, Zheng M, Feng Y, Hu K, Huang Y, Huang Q. Screening and identification of biomarkers in ascites related to intrinsic chemoresistance of serous epithelial ovarian cancers. PLoS One. 2012;7:e51256.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Clevers H. The cancer stem cell: premises, promises and challenges. Nat Med. 2011;17:313–9. https://doi.org/10.1038/nm.2304.

    Article  CAS  PubMed  Google Scholar 

  72. Prasetyanti PR, Medema JP. Intra-tumor heterogeneity from a cancer stem cell perspective. Mol Cancer. 2017;16:41.

    PubMed  PubMed Central  Google Scholar 

  73. Steg AD, Bevis KS, Katre AA, Ziebarth A, Dobbin ZC, Alvarez RD, Zhang K, Conner M, Landen CN. Stem cell pathways contribute to clinical chemoresistance in ovarian cancer. Clin Cancer Res. 2012;18:869–81.

    CAS  PubMed  Google Scholar 

  74. Pylvas-Eerola M, Liakka A, Puistola U, Koivunen J, Karihtala P. Cancer stem cell properties as factors predictive of chemoresistance in neoadjuvantly-treated patients with ovarian cancer. Anticancer Res. 2016;36:3425–31.

    CAS  PubMed  Google Scholar 

  75. Ottevanger PB. Ovarian cancer stem cells more questions than answers. Semin Cancer Biol. 2017;44:67.

    CAS  PubMed  Google Scholar 

  76. Kryczek I, Liu S, Roh M, Vatan L, Szeliga W, Wei S, Banerjee M, Mao Y, Kotarski J, Wicha MS, et al. Expression of aldehyde dehydrogenase and CD133 defines ovarian cancer stem cells. Int J Cancer. 2012;130:29–39. https://doi.org/10.1002/ijc.25967.

    Article  CAS  PubMed  Google Scholar 

  77. Le Page C, Ouellet V, Madore J, Ren F, Hudson TJ, Tonin PN, Provencher DM, Mes-Masson AM. Gene expression profiling of primary cultures of ovarian epithelial cells identifies novel molecular classifiers of ovarian cancer. Br J Cancer. 2006;94:436–45.

    PubMed  PubMed Central  Google Scholar 

  78. Le Page C, Puiffe ML, Meunier L, Zietarska M, de Ladurantaye M, Tonin PN, Provencher D, Mes-Masson AM. BMP-2 signaling in ovarian cancer and its association with poor prognosis. J Ovarian Res. 2009;2:4.

    PubMed  PubMed Central  Google Scholar 

  79. Huang RY, Chung VY, Thiery JP. Targeting pathways contributing to epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer. Curr Drug Targets. 2012;13:1649–53.

    CAS  PubMed  Google Scholar 

  80. Yoshida S, Furukawa N, Haruta S, Tanase Y, Kanayama S, Noguchi T, Sakata M, Yamada Y, Oi H, Kobayashi H. Expression profiles of genes involved in poor prognosis of epithelial ovarian carcinoma: a review. Int J Gynecol Cancer. 2009;19:992–7.

    PubMed  Google Scholar 

  81. Marchini S, Fruscio R, Clivio L, Beltrame L, Porcu L, Fuso Nerini I, Cavalieri D, Chiorino GC, Attoretti G, Mangioni C, et al. Resistance to platinum-based chemotherapy is associated with epithelial to mesenchymal transition in epithelial ovarian cancer. Eur J Cancer. 2013;49:520–30.

    CAS  PubMed  Google Scholar 

  82. van Zyl B, Tang D, Bowden N. Biomarkers of platinum resistance in ovarian cancer: what can we use to improve treatment. Endocr Relat Cancer. 2018;25(5):R303–18. https://erc.bioscientifica.com/view/journals/erc/25/5/ERC-17-0336.xml. Retrieved 9 Dec 2019.

    PubMed  Google Scholar 

  83. Choi YE, Meghani K, Brault ME, Leclerc L, He YJ, Day TA, Elias KM, Drapkin R, Weinstock DM, Dao F, et al. Platinum and PARP inhibitor resistance due to overexpression of microRNA-622 in BRCA1-mutant ovarian cancer. Cell Rep. 2016;14:429–39.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Vecchione A, Belletti B, Lovat F, Volinia S, Chiappetta G, Giglio S, Sonego M, Cirombella R, Onesti EC, Pellegrini P, et al. A microRNA signature defines chemoresistance in ovarian cancer through modulation of angiogenesis. PNAS. 2013;110:9845–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Boac BM, Xiong Y, Marchion DC, Abbasi F, Bush SH, Ramirez IJ, Khulpateea BR, Clair McClung E, Berry AL, Bou Zgheib N, et al. Micro-RNAs associated with the evolution of ovarian cancer cisplatin resistance. Gynecol Oncol. 2016;140:259–63.

    CAS  PubMed  Google Scholar 

  86. Ying HC, Xu HY, Lv J, Ying TS, Yang Q. MicroRNA signatures of platinum-resistance in ovarian cancer. Eur J Gynaecol Oncol. 2015;36:16–20.

    CAS  PubMed  Google Scholar 

  87. Yu X, Zheng H, Chan MT, Wu WK. Modulation of chemoresponsiveness to platinum-based agents by microRNAs in cancer. Am J Cancer Res. 2017;7:1769–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474(7353):609–15.

    Google Scholar 

  89. Ramus SJ, Harrington PA, Pye C, et al. Contribution of BRCA1 and BRCA2 mutations to inherited ovarian cancer. Hum Mutat. 2007;28(12):1207–15.

    CAS  PubMed  Google Scholar 

  90. Phelan CM, Kuchenbaecker KB, Tyrer JP, et al. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer. Nat Genet. 2017;49(5):680–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Yeung TL, Leung CS, Yip KP, et al. Cellular and molecular processes in ovarian cancer metastasis. A review in the theme: cell and molecular processes in cancer metastasis. Am J Physiol Cell Physiol. 2015;309(7):C444–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Wang X, Zhu Q, Lin Y, et al. Crosstalk between TEMs and endothelial cells modulates angiogenesis and metastasis via IGF1-IGF1R signalling in epithelial ovarian cancer. Br J Cancer. 2017;117(9):1371–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Hagemann T, Wilson J, Kulbe H, et al. Macrophages induce invasiveness of epithelial cancer cells via NF-kB and JNK. J Immunol. 2005;175(2):1197–205.

    CAS  PubMed  Google Scholar 

  94. Wang X, Deavers M, Patenia R, et al. Monocyte/macrophage and T-cell infiltrates in peritoneum of patients with ovarian cancer or benign pelvic disease. J Transl Med. 2006;4(1):30.

    PubMed  PubMed Central  Google Scholar 

  95. Penet MF, Krishnamachary B, Wildes FB, Mironchik Y, Hung CF, Wu TC, Bhujwalla ZM. Ascites volumes and the ovarian cancer microenvironment. Front Oncol. 2018;8:595. https://doi.org/10.3389/fonc.2018.00595.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Ahmed N, Stenvers KL. Getting to know ovarian cancer ascites: opportunities for targeted therapy-based translational research. Front Oncol. 2013;3:256. https://doi.org/10.3389/fonc.2013.00256.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Carr NJ, Bibeau F, Bradley RF, Dartigues P, Feakins RM, Geisinger KR, et al. The histopathological classification, diagnosis and differential diagnosis of mucinous appendiceal neoplasms, appendiceal adenocarcinomas and pseudomyxoma peritonei. Histopathology. 2017;71(6):847–58. https://doi.org/10.1111/his.13324. Epub 19 Sept 2017.

    Article  PubMed  Google Scholar 

  98. Saarinen L, Nummela P, Leinonen H, Heiskanen A, Thiel A, Halgund C, Lepisto A, et al. Glycomic profiling highlights increased fucosylation in pseudomyxoma peritonei. Mol Cell Proteomics. 2018;17:2107–18. https://doi.org/10.1074/mcp.RA118.000615.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Choudry HA, O’Malley ME, Guo ZS, Zeh HJ, Bartlett DL. Mucin as a therapeutic target in pseudomyxoma peritonei. J Surg Oncol. 2012;106:911–7.

    CAS  PubMed  Google Scholar 

  100. Hugen N, Brown G, Glynne-Jones R, de Wilt JH, Nagtegaal ID. Advances in the care of patients with mucinous colorectal cancer. Nat Rev Clin Oncol. 2016;13:361–9.

    CAS  PubMed  Google Scholar 

  101. Amini A, Masoumi-Moghaddam S, Ehteda A, Morris DL. Secreted mucins in pseudomyxoma peritonei: pathophysiological significance and potential therapeutic prospects. Orphanet J Rare Dis. 2014;9:71.

    PubMed  PubMed Central  Google Scholar 

  102. O’Connell JT, Tomlinson JS, Roberts AA, McGonigle KF, Barsky SH. Pseudomyxoma peritonei is a disease of MUC2-expressing goblet cells. Am J Pathol. 2002;161:551–64.

    PubMed  PubMed Central  Google Scholar 

  103. Hugen N, Simons M, Halilovic A, van der Post RS, Bogers AJ, Marijnissen-van Zanten MA, de Wilt JH, Nagtegaal ID. The molecular background of mucinous carcinoma beyond MUC2. J Pathol Clin Res. 2015;1:3–17.

    CAS  PubMed  Google Scholar 

  104. Alakus H, Babicky ML, Ghosh P, Yost S, Jepsen K, Dai Y, Arias A, Samuels ML, Mose ES, Schwab RB, Peterson MR, Lowy AM, Frazer KA, et al. Genome-wide mutational landscape of mucinous carcinomatosis peritonei of appendiceal origin. Genome Med. 2014;6:43.

    PubMed  PubMed Central  Google Scholar 

  105. Liu X, Mody K, de Abreu FB, Pipas JM, Peterson JD, Gallagher TL, Suriawinata AA, Ripple GH, Hourdequin KC, Smith KD, Barth RJ Jr, Colacchio TA, Tsapakos MJ, et al. Molecular profiling of appendiceal epithelial tumors using massively parallel sequencing to identify somatic mutations. Clin Chem. 2014;60:1004–11.

    CAS  PubMed  Google Scholar 

  106. Gatalica Z, Loggie B. COX-2 expression in pseudomyxoma peritonei. Cancer Lett. 2006;244:86–90.

    CAS  PubMed  Google Scholar 

  107. Dilly AK, Honick BD, Lee YJ, Guo ZS, Zeh HJ, Bartlett DL, Choudry HA. Targeting G-protein coupled receptor-related signaling pathway in a murine xenograft model of appendiceal pseudomyxoma peritonei. Oncotarget. 2017;8(63):106888–900. https://doi.org/10.18632/oncotarget.22455.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Grizzi F, Cananzi F, Battista S, Brambilla T, Quehajaj D, Chiriva Internatti M, et al. Immunohistochemical features of the pseudomyxoma peritonei microenvironment: an opportunity for clinicians. http://www.aqch.com›toc›auto_article_process. Accessed 3/10/2019.

  109. Valle SJ, Akhter J, Mekkawy AH, Lodh S, Pillai K, Badar S, Glenn D, Power M, Liauw W, Morris DL. A novel treatment of bromelain and acetylcysteine (BromAc) in patients with peritoneal mucinous tumours: a phase I first in man study. Eur J Surg Oncol. 2019. pii: S0748-7983(19)30913-8. https://doi.org/10.1016/j.ejso.2019.10.033. [Epub ahead of print].

  110. Reitz D, Gerger A, Seidel J, Kornprat P, Samonigg H, Stotz M, Szkandera J, Pichler M. Combination of tumour markers CEA and CA19–9 improves the prognostic prediction in patients with pancreatic cancer. J Clin Pathol. 2015;68:427–33.

    CAS  PubMed  Google Scholar 

  111. Stojkovic Lalosevic M, Stankovic S, Stojkovic M, Markovic V, Dimitrijevic I, Lalosevic J, Petrovic J, Brankovic M, Pavlovic Markovic A, Krivokapic Z. Can preoperative CEA and CA19-9 serum concentrations suggest metastatic disease in colorectal cancer patients? Hell J Nucl Med. 2017;20:41–5.

    PubMed  Google Scholar 

  112. Wang W, Chen XL, Zhao SY, Xu YH, Zhang WH, Liu K, Chen XZ, Yang K, Zhang B, Chen ZX, Chen JP, Zhou ZG, Hu JK. Prognostic significance of preoperative serum CA125, CA19-9 and CEA in gastric carcinoma. Oncotarget. 2016;7:35423–36.

    PubMed  PubMed Central  Google Scholar 

  113. Song Y, Wang B, He M, Bai M, Liang G. Circulating serum microRNAs as diagnostic biomarkers for pseudomyxoma peritonei. Int J Clin Exp Med. 2018;11(11):12340–6.

    CAS  Google Scholar 

  114. Fang Z, Tang J, Bai Y, Lin H, You H, Jin H, Lin L, You P, Li J, Dai Z, Liang X, Su Y, Hu Q, Wang F, Zhang ZY. Plasma levels of microRNA-24, microRNA-320a, and microRNA-423-5p are potential biomarkers for colorectal carcinoma. J Exp Clin Cancer Res. 2015;34:86.

    PubMed  PubMed Central  Google Scholar 

  115. Bobowicz M, Skrzypski M, Czapiewski P, Marczyk M, Maciejewska A, Jankowski M, Szulgo-Paczkowska A, Zegarski W, Pawłowski R, Polańska J, Biernat W, Jaśkiewicz J, Jassem J. Prognostic value of 5-microRNA based signature in T2-T3N0 colon cancer. Clin Exp Metastasis. 2016;33:765–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Du L, Jiang X, Duan W, Wang R, Wang L, Zheng G, Yan K, Wang L, Li J, Zhang X, Pan H, Yang Y, Wang C. Cell-free microRNA expression signatures in urine serve as novel noninvasive biomarkers for diagnosis and recurrence prediction of bladder cancer. Oncotarget. 2017;8:40832–42.

    PubMed  PubMed Central  Google Scholar 

  117. Fan KL, Zhang HF, Shen J, Zhang Q, Li XL. Circulating microRNAs levels in Chinese heart failure patients caused by dilated cardiomyopathy. Indian Heart J. 2013;65:12–6.

    PubMed  PubMed Central  Google Scholar 

  118. Yan H, Ma F, Zhang Y, Wang C, Qiu D, Zhou K, Hua Y, Li Y. miRNAs as biomarkers for diagnosis of heartfailure-A systematic review and meta-analysis. Medicine. 2017;96:e6825.

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Kong YW, Ferland-McCollough D, Jackson TJ, Bushell M. microRNAs in cancer management. Lancet Oncol. 2012;13:e249–58.

    CAS  PubMed  Google Scholar 

  120. Tashian RE. Genetics of the mammalian carbonic anhydrases. Adv Genet. 1992;30:321–56.

    CAS  PubMed  Google Scholar 

  121. Parkkila S, Parkkila AK, Juvonen T, Lehto VP, Rajaniemi H. Immunohistochemical demonstration of the carbonic anhydrase isoenzymes I and II in pancreatic tumours. Histochem J. 1995;27:133–8.

    CAS  PubMed  Google Scholar 

  122. Kivela AJ, Saarnio J, Karttunen TJ, Kivela J, Parkkila AK, Pastorekova S, et al. Differential expression of cytoplasmic carbonic anhydrases, CA I and II, and membrane-associated isozymes, CA IX and XII, in normal mucosa of large intestine and in colorectal tumors. Dig Dis Sci. 2001;46:2179–86.

    CAS  PubMed  Google Scholar 

  123. Hu X, Huang Z, Liao Z, He C, Fang X. Low CA II expression is associated with tumor aggressiveness and poor prognosis in gastric cancer patients. Int J Clin Exp Pathol. 2014;7:6716–24.

    PubMed  PubMed Central  Google Scholar 

  124. Kuo WH, Chiang WL, Yang SF, Yeh KT, Yeh CM, Hsieh YS, et al. The differential expression of cytosolic carbonic anhydrase in human hepatocellular carcinoma. Life Sci. 2003;73:2211–23.

    CAS  PubMed  Google Scholar 

  125. Järvinen P, Kivelä AJ, Nummela P, Lepistö A, Ristimäki A, Parkkila S. Carbonic anhydrase II: a novel biomarker for pseudomyxoma peritonei. APMIS. 2017;125(3):207–12. https://doi.org/10.1111/apm.12653.

    Article  CAS  PubMed  Google Scholar 

  126. Kabbani W, Houlihan PS, Luthra R, Hamilton SR, Rashid A. Mucinous and nonmucinous appendiceal adenocarcinomas: different clinicopathological features but similar genetic alterations. Mod Pathol. 2002;15(6):599–605.

    PubMed  Google Scholar 

  127. Szych C, Staebler A, Connolly DC, Wu R, Cho KR, Ronnett BM. Molecular genetic evidence supporting the clonality and appendiceal origin of pseudomyxoma peritonei in women. Am J Pathol. 1999;154(6):1849–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Zauber P, Berman E, Marotta S, Sabbath-Solitare M, Bishop T. Ki-ras gene mutations are invariably present in low-grade mucinous tumours of the vermiform appendix. Scand J Gastroenterol. 2011;46(7–8):869–74.

    CAS  PubMed  Google Scholar 

  129. Nummela P, Saarinen L, Thiel A, Järvinen P, Lehtonen R, Lepistö A, Järvinen H, Aaltonen LA, Hautaniemi S, Ristimäki A. Genomic profile of pseudomyxoma peritonei analyzed using next-generation sequencing and immunohistochemistry. Int J Cancer. 2015;136:E282–9.

    CAS  PubMed  Google Scholar 

  130. Austin F, Mavanur A, Sathaiah M, Steel J, Lenzner D, Ramalingam L, Holtzman M, Ahrendt S, Pingpank J, Zeh HJ, Bartlett DL, Choudry HA. Aggressive management of peritoneal carcinomatosis from mucinous appendiceal neoplasms. Ann Surg Oncol. 2012;19(5):1386–93. https://doi.org/10.1245/s10434-012-2241-6.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Andreyev HJ, Norman AR, Cunningham D, et al. Kirsten ras mutations in patients with colorectal cancer: the multicenter “RASCAL” study. J Natl Cancer Inst. 1998;90:675.

    CAS  PubMed  Google Scholar 

  132. Vogelstein B, Fearon ER, Hamilton SR, et al. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988;319:525.

    CAS  PubMed  Google Scholar 

  133. Bazan V, Migliavacca M, Zanna I, et al. Specific codon 13 K-ras mutations are predictive of clinical outcome in colorectal cancer patients, whereas codon 12 K-ras mutations are associated with mucinous histotype. Ann Oncol. 2002;13:1438.

    CAS  PubMed  Google Scholar 

  134. Ogino S, Brahmandam M, Cantor M, et al. Distinct molecular features of colorectal carcinoma with signet ring cell component and colorectal carcinoma with mucinous component. Mod Pathol. 2006;19:59.

    CAS  PubMed  Google Scholar 

  135. Wistuba II, Behrens C, Albores-Saavedra J, et al. Distinct K-ras mutation pattern characterizes signet ring cell colorectal carcinoma. Clin Cancer Res. 2003;9:3615.

    CAS  PubMed  Google Scholar 

  136. Paraskevakou H, Saetta A, Skandalis K, et al. Morphologicalhistochemical study of intestinal carcinoids and K-ras mutation analysis in appendiceal carcinoids. Pathol Oncol Res. 1999;5:205.

    CAS  PubMed  Google Scholar 

  137. Ramnani DM, Wistuba II, Behrens C, et al. K-ras and p53 mutations in the pathogenesis of classical and goblet cell carcinoids of the appendix. Cancer. 1999;86:14.

    CAS  PubMed  Google Scholar 

  138. Vaughn CP, Zobell SD, Furtado LV, et al. Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer. Genes Chromosomes Cancer. 2011;50:307.

    CAS  PubMed  Google Scholar 

  139. Shetty S, Thomas P, Ramanan B, et al. KRAS mutations and p53 overexpression in pseudomyxoma peritonei: association with phenotype and prognosis. J Surg Res. 2013;180:97–10.

    CAS  PubMed  Google Scholar 

  140. Pietrantonio F, Perrone F, Mennitto A, Gleeson EM, Milione M, Tamborini E, Busico A, Settanni G, Berenato R, Caporale M, Morano F, Bossi I, Pellegrinelli A, Di Bartolomeo M, de Braud F, Baratti D, Bowne WB, Kusamura S, Deraco M. Toward the molecular dissection of peritoneal pseudomyxoma. Ann Oncol. 2016;27(11):2097–103. Epub 8 Aug 2016.

    CAS  PubMed  Google Scholar 

  141. Vincenzi B, Cremolini C, Sartore-Bianchi A, et al. Prognostic significance of K-Ras mutation rate in metastatic colorectal cancer patients. Oncotarget. 2015;6:31604–12.

    PubMed  PubMed Central  Google Scholar 

  142. Landis CA, Masters SB, Spada A, Pace AM, Bourne HR, Vallar L. GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours. Nature. 1989;340(6236):692–6.

    CAS  PubMed  Google Scholar 

  143. Lyons J, Landis CA, Harsh G, Vallar L, Grunewald K, Feichtinger H, Duh QY, Clark OH, Kawasaki E, Bourne HR, et al. Two G protein oncogenes in human endocrine tumors. Science. 1990;249(4969):655–9.

    CAS  PubMed  Google Scholar 

  144. Nishikawa G, Sekine S, Ogawa R, et al. Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms. Br J Cancer. 2013;108(4):951–8. https://doi.org/10.1038/bjc.2013.47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Furukawa T, Kuboki Y, Tanji E, Yoshida S, Hatori T, Yamamoto M, Shibata N, Shimizu K, Kamatani N, Shiratori K. Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas. Sci Rep. 2011;1:161.

    PubMed  PubMed Central  Google Scholar 

  146. Matsubara A, Sekine S, Kushima R, Ogawa R, Taniguchi H, Tsuda H, Kanai Y. Frequent GNAS and KRAS mutations in pyloric gland adenoma of the stomach and duodenum. J Pathol. 2013;229(4):579–87. https://doi.org/10.1002/path.4153.

    Article  CAS  PubMed  Google Scholar 

  147. Wu J, Matthaei H, Maitra A, et al. Papadopoulos N, Hruban RH, Vogelstein B. Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. Sci Transl Med. 2011;3(92):92ra66. https://doi.org/10.1126/scitranslmed.3002543. PMID: 21775669; PMCID: PMC3160649

  148. Sio TT, Mansfield AS, Grotz TE, et al. Concurrent MCL1 and JUN amplification in pseudomyxoma peritonei: a comprehensive genetic profiling and survival analysis. J Hum Genet. 2014;59:124–8.

    CAS  PubMed  Google Scholar 

  149. Singhi AD, Davison JM, Choudry HA, et al. GNAS is frequently mutated in both low-grade and high-grade disseminated appendiceal mucinous neoplasms but does not affect survival. Hum Pathol. 2014;45:1737–43.

    CAS  PubMed  Google Scholar 

  150. Hollstein M, Sidransky D, Vogelstein B, et al. P53 mutations in human cancers. Science. 1991;253:49.

    CAS  PubMed  Google Scholar 

  151. Nigro JM, Baker SJ, Preisinger AC, et al. Mutations in the p53 gene occur in diverse human tumour types. Nature. 1989;342:705.

    CAS  PubMed  Google Scholar 

  152. Noguchi R, Yano H, Gohda Y, et al. Molecular profiles of high-grade and low-grade pseudomyxoma peritonei. Cancer Med. 2015;4(12):1809–16. https://doi.org/10.1002/cam4.542.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Ahnen DJ, Feigl P, Quan G, et al. Ki-ras mutation and p53 overexpression predict the clinical behavior of colorectal cancer: a southwest oncology group study. Cancer Res. 1998;58:1149.

    CAS  PubMed  Google Scholar 

  154. Perraud A, Akil H, Nouaille M, et al. Expression of p53 and DR5 in normal and malignant tissues of colorectal cancer: correlation with advanced stages. Oncol Rep. 2011;26:1091.

    PubMed  Google Scholar 

  155. Remvikos Y, Tominaga O, Hammel P, et al. Increased p53 protein content of colorectal tumours correlates with poor survival. Br J Cancer. 1992;66:758.

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Sun XF, Carstensen JM, Zhang H, et al. Prognostic significance of cytoplasmic p53 oncoprotein in colorectal adenocarcinoma. Lancet. 1992;340:1369.

    CAS  PubMed  Google Scholar 

  157. Hamelin R, Laurent-Puig P, Olschwang S, et al. Association of p53 mutations with short survival in colorectal cancer. Gastroenterology. 1994;106:42.

    CAS  PubMed  Google Scholar 

  158. Huh JW, Lee JH, Kim HR. Expression of p16, p53, and ki-67 in colorectal adenocarcinoma: a study of 356 surgically resected cases. Hepatogastroenterology. 2010;57:734.

    PubMed  Google Scholar 

  159. Conlin A, Smith G, Carey FA, et al. The prognostic significance of K-ras, p53, and APC mutations in colorectal carcinoma. Gut. 2005;54(9):1283–6. https://doi.org/10.1136/gut.2005.066514. Epub 2005 Apr 20. PMID: 15843421; PMCID: PMC1774675.

  160. O’Dowd G, Gosney JR. Absence of overexpression of p53 protein by intestinal carcinoid tumours. J Pathol. 1995;175:403.

    PubMed  Google Scholar 

  161. Gleeson EM, Feldman R, Mapow BL, Mackovick LT, Ward KM, Morano WF, Rubin RR, Bowne WB. Appendix-derived pseudomyxoma peritonei (PMP): molecular profiling toward treatment of a rare malignancy. Am J Clin Oncol. 2018;41(8):777–83. https://doi.org/10.1097/COC.0000000000000376.

    Article  CAS  PubMed  Google Scholar 

  162. Roberts DL, O’Dwyer ST, Stern PL, et al. Global gene expression in pseudomyxoma peritonei, with parallel development of two immortalized cell lines. Oncotarget. 2015;6:10786–800.

    PubMed  PubMed Central  Google Scholar 

  163. Levine EA, Votanopoulos KI, Qasem SA, et al. Prognostic molecular subtypes of low-grade cancer of the appendix. J Am College Surg. 2016;222:493–503.

    Google Scholar 

  164. Singh J, Sharma A, Ahuja N. Genomics of peritoneal surface malignancies. J Peritoneum [Internet]. 12 Jul 2017 [cited 10 Dec 2019];2(2). Available from: http://www.jperitoneum.org/index.php/joper/article/view/62.

  165. Markowitz SD, Bertagnolli MM. Molecular origins of cancer: molecular basis of colorectal cancer. N Engl J Med. 2009;361:2449–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Herman JG, Umar A, Polyak K, et al. Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci U S A. 1998;95:6870–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Hugen N, van de Velde CJ, de Wilt JH, et al. Metastatic pattern in colorectal cancer is strongly influenced by histological sub-type. Ann Oncol. 2014;25:651–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  168. Hewish M, Lord CJ, Martin SA, et al. Mismatch repair deficient colorectal cancer in the era of personalized treatment. Nat Rev Clin Oncol. 2010;7:197–208.

    PubMed  Google Scholar 

  169. Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  170. Shelygin YA, Pospekhova NI, Shubin VP, et al. Epithelial-mesechymal transition and somatic alteration in colorectal cancer with and without peritoneal carcinomatosis. Biomed Res Int. 2014;2014:629496.

    CAS  PubMed  PubMed Central  Google Scholar 

  171. Weisenberger DJ, Siegmund KD, Campan M, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 2006;38:787–93.

    CAS  PubMed  Google Scholar 

  172. Toyota M, Ahuja N, Ohe-Toyota M, et al. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A. 1999;96:8681–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  173. McCubrey JA, Steelman LS, Chappell WH, et al. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta. 2007;1773:1263–84.

    CAS  PubMed  Google Scholar 

  174. Pietrantonio F, Petrelli F, Coinu A, et al. Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab: a meta-analysis. Eur J Cancer. 2015;51:587–94.

    CAS  PubMed  Google Scholar 

  175. Karapetis CS, Khambata-Ford S, Jonker DJ, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008;359:1757–65.

    CAS  PubMed  Google Scholar 

  176. Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487:330–7.

    Google Scholar 

  177. Kavuri SM, Jain N, Galimi F, et al. HER2 activating mutations are targets for colorectal cancer treatment. Cancer Discov. 2015;5:832–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  178. Sartore-Bianchi A, Trusolino L, Martino C, et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016;17:738–46.

    CAS  PubMed  Google Scholar 

  179. Lee IK, Kim DH, Gorden DL, et al. Prognostic value of CEA and CA 19-9 tumor markers combined with cytology from peritoneal fluid in colorectal cancer. Ann Surg Oncol. 2009;16(4):861–70.

    PubMed  Google Scholar 

  180. Bhullar DS, Barriuso J, Mullamitha S, Saunders MP, O’Dwyer ST, Aziz O. Biomarker concordance between primary colorectal cancer and its metastases. EBioMedicine. 2019;40:363–74. https://doi.org/10.1016/j.ebiom.2019.01.050. Epub 4 Feb 2019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Takakura Y, Ikeda S, Imaoka Y, Urushihara T, Itamoto T. An elevated preoperative serum carbohydrate antigen 19-9 level is a significant predictor for peritoneal dissemination and poor survival in colorectal cancer. Colorectal Dis. 2015;17(5):417–25.

    CAS  PubMed  Google Scholar 

  182. Ahadi M, Tehranian S, Memar B, et al. Diagnostic value of carcinoembryonic antigen in malignancy-related ascites: systematic review and meta-analysis. Acta Gastroenterol Belg. 2014;77:418–24.

    PubMed  Google Scholar 

  183. Huang CJ, Jiang JK, Chang SC, Lin JK, Yang SH. Serum CA125 concentration as a predictor of peritoneal dissemination of colorectal cancer in men and women. Medicine (Baltimore). 2016;95(47):e5177.

    CAS  Google Scholar 

  184. Kaneko M, Ishihara S, Murono K, et al. Carbohydrate antigen 19-9 predicts synchronous peritoneal carcinomatosis in patients with colorectal cancer. Anticancer Res. 2017;37(2):865–70.

    CAS  PubMed  Google Scholar 

  185. Cashin PH, Graf W, Nygren P, Mahteme H. Patient selection for cytoreductive surgery in colorectal peritoneal carcinomatosis using serum tumor markers: an observational cohort study. Ann Surg. 2012;256(6):1078–83.

    PubMed  Google Scholar 

  186. Ozawa H, Kotake K, Kobayashi H, Kobayashi H, Sugihara K. Prognostic factors for peritoneal carcinomatosis originating from colorectal cancer: an analysis of 921 patients from a multi-institutional database. Surg Today. 2014;44(9):1643–50.

    PubMed  Google Scholar 

  187. Chia CS, Glehen O, Bakrinetal N. Intraperitonealvascular endothelial growth factor: a prognostic factor and the potential for intraperitoneal bevacizumab use in peritoneal surface malignancies. Ann Surg Oncol. 2015;22(Suppl 3):880–7.

    Google Scholar 

  188. Bong TSH, Tan GHC, Chia C, Soo KC, Teo MCC. Preoperative platelet-lymphocyte ratio is an independent prognostic marker and superior to carcinoembryonic antigen in colorectal peritoneal carcinomatosis patients undergoing cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy. Int J Clin Oncol. 2017;22(3):511–8.

    CAS  PubMed  Google Scholar 

  189. Huo YR, Huang Y, Liauw W, Zhao J, Morris DL. Prognostic value of carcinoembryonic antigen (CEA), AFP, CA19-9 and CA125 for patients with colorectal cancer with peritoneal carcinomatosis treated by cytoreductive surgery and intraperitoneal chemotherapy. Anticancer Res. 2016;36(3):1041–9.

    CAS  PubMed  Google Scholar 

  190. Green DE, Jayakrishnan TT, Hwang M, Pappas SG, Gamblin TC, Turaga KK. Immunohistochemistry—microarray analysis of patients with peritoneal metastases of appendiceal or colorectal origin. Front Surg. 2015;1:50.

    PubMed  PubMed Central  Google Scholar 

  191. Sasaki Y, Hamaguchi T, Yamada Y, et al. Value of KRAS, BRAF, and PIK3CA mutations and survival benefit from systemic chemotherapy in colorectal peritoneal carcinomatosis. Asian Pac J Cancer Prev. 2016;17(2):539–43.

    PubMed  Google Scholar 

  192. Massalou D, Benizri E, Chevallier A, et al. Peritoneal carcinomatosis of colorectal cancer: novel clinical and molecular outcomes. Am J Surg. 2017;213(2):377–87.

    PubMed  Google Scholar 

  193. Yokota T, Ura T, Shibataetal N. BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer. Br J Cancer. 2011;104(5):856–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  194. Ihemelandu C. Inflammation-based prognostic scores: utility in prognostication and patient selection for cytoreduction and perioperative intraperitoneal chemotherapy in patients with peritoneal metastasis of colonic origin. Ann Surg Oncol. 2017;24(4):884–9.

    PubMed  Google Scholar 

  195. Harrison LE, Bryan M, Pliner L, Saunders T. Phase I trial of pegylated liposomal doxorubicin with hyperthermic intraperitoneal chemotherapy in patients undergoing cytoreduction for advanced intra-abdominal malignancy. Ann Surg Oncol. 2008;15(5):1407–13.

    PubMed  Google Scholar 

  196. de Cuba EMV, de Hingh IHJT, Sluiter NR, et al. Angiogenesis-related markers and prognosis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for metastatic colorectal cancer. Ann Surg Oncol. 2016;23(5):1601–8.

    PubMed  PubMed Central  Google Scholar 

  197. Sluiter NR, de Cuba EMV, Kwakman R, et al. Versican and vascular endothelial growth factor expression levels in peritoneal metastases from colorectal cancer are associated with survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Clin Exp Metastasis. 2016;33(4):297–307.

    CAS  PubMed  PubMed Central  Google Scholar 

  198. Guinney J, Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa E, Melo F, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21(11):1350–6. https://doi.org/10.1038/nm.3967. Epub 12 Oct 2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Ubink I, van Eden WJ, Snaebjornsson P, et al. Histopathological and molecular classification of colorectal cancer and corresponding peritoneal metastases. Br J Surg. 2018;105(2):e204–11.

    CAS  PubMed  Google Scholar 

  200. Koumpa FS, Xylas D, Konopka M, et al. Colorectal peritoneal metastases: a systematic review of current and emerging trends in clinical and translational research. Gastroenterol Res Pract. 2019;2019:5180895, 30 p. https://doi.org/10.1155/2019/5180895.

  201. Varghese S, Burness M, Xu H, Beresnev T, Pingpank J, Alexander HR. Site-specific gene expression profiles and novel molecular prognostic factors in patients with lower gastrointestinal adenocarcinoma diffusely metastatic to liver or peritoneum. Ann Surg Oncol. 2007;14(12):3460–71.

    PubMed  Google Scholar 

  202. Logan-Collins JM, Lowy AM, Robinson-Smith TM, et al. VEGF expression predicts survival in patients with peritoneal surface metastases from mucinous adenocarcinoma of the appendix and colon. Ann Surg Oncol. 2008;15(3):738–44.

    PubMed  Google Scholar 

  203. Lin BR, Chang CC, Chen RJC, et al. Connective tissue growth factor acts as a therapeutic agent and predictor for peritoneal carcinomatosis of colorectal cancer. Clin Cancer Res. 2011;17(10):3077–88.

    CAS  PubMed  Google Scholar 

  204. Arienti C, Tesei A, Verdecchiaetal GM. Role of conventional chemosensitivity test and tissue biomarker expression in predicting response to treatment of peritoneal carcinomatosis from colon cancer. Clin Colorectal Cancer. 2013;12(2):122–7.

    CAS  PubMed  Google Scholar 

  205. Kwakman R, deCuba EMV, deWinteretal JP. Tailoring heated intraperitoneal mitomycin C for peritoneal metastases originating from colorectal carcinoma: a translational approach to improve survival. Br J Cancer. 2015;112(5):851–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  206. Shannon NB, Tan JW, Tan HL, Wang W, Chen Y, Lim HJ, Tan QX, Hendrikson J, Ng WH, Loo LY, Skanthakumar T, Wasudevan SD, Kon OL, Lim TKH, Tan GHC, Chia CS, Soo KC, Ong CJ, Teo MCC. A set of molecular markers predicts chemosensitivity to Mitomycin-C following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis. Sci Rep. 2019;9(1):10572. https://doi.org/10.1038/s41598-019-46819-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Pelz JOW, Stojadinovic A, Nissan A, Hohenberger W, Esquivel J. Evaluation of a peritoneal surface disease severity score in patients with colon cancer with peritoneal carcinomatosis. J Surg Oncol. 2009;99:9–15. https://doi.org/10.1002/jso.21169.

    Article  PubMed  Google Scholar 

  208. Esquivel J, Lowy AM, Markman M, Chua T, Pelz J, Baratti D, et al. The American Society of Peritoneal Surface Malignancies (ASPSM) multiinstitution evaluation of the peritoneal surface disease severity score (PSDSS) in 1,013 patients with colorectal cancer with peritoneal carcinomatosis. Ann Surg Oncol. 2014;21(13):4195–201. https://doi.org/10.1245/s10434-014-3798-z.

    Article  PubMed  Google Scholar 

  209. Ng JL, Ong WS, Chia CS, Tan GHC, Soo K-C, Teo MCC. Prognostic relevance of the peritoneal surface disease severity score compared to the peritoneal cancer index for colorectal peritoneal carcinomatosis. Int J Surg Oncol. 2016;2016:2495131, 7. https://doi.org/10.1155/2016/2495131.

  210. Arjona-Sanchez A, Rodriguez-Ortiz L, Baratti D, Schneider MA, Gutiérrez-Calvo A, García-Fadrique A, et al. RAS mutation decreases overall survival after optimal cytoreductive surgery and hyperthermic intraperitoneal chemotherapy of colorectal peritoneal metastasis: a modification proposal of the peritoneal surface disease severity score. Ann Surg Oncol. 2019;26(8):2595–604. https://doi.org/10.1245/s10434-019-07378-9. Epub 20 May 2019.

    Article  CAS  PubMed  Google Scholar 

  211. Schneider MA, Eden J, Pache B, Laminger F, Lopez-Lopez V, Steffen T, Hübner M, Kober F, Roka S, Campos PC, Roth L, Gupta A, Siebenhüner A, Kepenekian V, Passot G, Gertsch P, Glehen O, Lehmann K. Mutations of RAS/RAF proto-oncogenes impair survival after cytoreductive surgery and HIPEC for peritoneal metastasis of colorectal origin. Ann Surg. 2018;268(5):845–53. https://doi.org/10.1097/SLA.0000000000002899.

    Article  PubMed  Google Scholar 

  212. Lim B, Kim C, Kim JH, Kwon WS, Lee WS, Kim JM, Park JY, Kim HS, Park KH, Kim TS, Park JL, Chung HC, Rha SY, Kim SY. Genetic alterations and their clinical implications in gastric cancer peritoneal carcinomatosis revealed by whole-exome sequencing of malignant ascites. Oncotarget. 2016;7(7):8055–66. https://doi.org/10.18632/oncotarget.6977.

    Article  PubMed  PubMed Central  Google Scholar 

  213. Kusamura S, Baratti D, Zaffaroni N, et al. Pathophysiology and biology of peritoneal carcinomatosis. World J Gastrointest Oncol. 2010;2(1):12–8.

    PubMed  PubMed Central  Google Scholar 

  214. Jayne D. Molecular biology of peritoneal carcinomatosis. Cancer Treat Res. 2007;134:21–33.

    CAS  PubMed  Google Scholar 

  215. Zhang J, Huang JY, Chen YN, et al. Whole genome and transcriptome sequencing of matched primary and peritoneal metastatic gastric carcinoma. Sci Rep. 2015;5:13750. https://doi.org/10.1038/srep13750.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Waaijer CJ, de Andrea CE, Hamilton A, et al. Cartilage tumour progression is characterized by an increased expression of heparan sulphate 6O-sulphation-modifying enzymes. Virchows Arch. 2012;461(4):475–81.

    CAS  PubMed  Google Scholar 

  217. Ohi M, Mori K, Toyiyama Y, Mohri Y, Okigami M, Yasuda H, et al. Preoperative prediction of peritoneal metastasis in gastric cancer as an indicator for neoadjuvant treatment. Anticancer Res. 2015;35(6):3511–8.

    CAS  PubMed  Google Scholar 

  218. Mura G, Verdelli B. The features of peritoneal metastases from gastric cancer. J Cancer Metastasis Treatm. 2016;2:365. https://doi.org/10.20517/2394-4722.2016.19.

    Article  CAS  Google Scholar 

  219. Takeno A, et al. Gene expression profile prospectively predicts peritoneal relapse after curative surgery of gastric cancer. Ann Surg Oncol. 2010;17:1033–42. https://doi.org/10.1245/s10434-009-0854-1.

    Article  PubMed  Google Scholar 

  220. Zeng R, Li B, Huang J, Zhong M, Li L, Duan C, Zeng S, Huang J, Liu W, Lu J, Tang Y, Zhou L, Liu Y, Li J, He Z, Wang Q, Dai Y. Lysophosphatidic acid is a biomarker for peritoneal carcinomatosis of gastric cancer and correlates with poor prognosis. Genet Test Mol Biomarkers. 2017;21(11):641–8. https://doi.org/10.1089/gtmb.2017.0060. Epub 14 Sept 2017.

    Article  CAS  PubMed  Google Scholar 

  221. Chen C, Shi C, Huang X, et al. Molecular profiles and metastasis markers in Chinese patients with gastric carcinoma. Sci Rep. 2019;9:13995. https://doi.org/10.1038/s41598-019-50171-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Wang R, Song S, Harada K, Ghazanfari Amlashi F, Badgwell B, Pizzi MP, Xu Y, Zhao W, Dong X, Jin J, Wang Y, Scott A, et al. Multiplex profiling of peritoneal metastases from gastric adenocarcinoma identified novel targets and molecular subtypes that predict treatment response. Gut. 2020;69(1):18–31. https://doi.org/10.1136/gutjnl-2018-318070. Epub 6 Jun 2019.

    Article  PubMed  Google Scholar 

  223. Kitayama J, Ishigami H, Yamaguchi H, Emoto S, Yamashita H, Seto Y, Matsusaki K, Watanabe T. Tumor cells/leukocytes ratio (TLR) in peritoneal fluids as a biomarker in patients with peritoneal metastasis of gastric cancer. J Clin Oncol. 2014;32(15 Suppl):3039.

    Google Scholar 

  224. Bridda A, Padoan I, Mencarelli R, et al. Peritoneal mesothelioma: a review. MedGenMed. 2007;92:32.

    Google Scholar 

  225. Boffetta P. Epidemiology of peritoneal mesothelioma: a review. Ann Oncol. 2007;18:985–90.

    CAS  PubMed  Google Scholar 

  226. 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. https://doi.org/10.21037/tlcr.2017.05.06.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  227. Creaney J, Sneddon S, Dick IM, et al. Comparison of the diagnostic accuracy of the MSLN gene products, mesothelin and megakaryocyte potentiating factor, as biomarkers for mesothelioma in pleural effusions and serum. Dis Markers. 2013;35:119–27. https://doi.org/10.1155/2013/874212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  228. Creaney J, Dick IM, Meniawy TM, et al. Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma. Thorax. 2014;69:895–902. https://doi.org/10.1136/thoraxjnl-2014-205205.

    Article  PubMed  Google Scholar 

  229. Murali R, Wiesner T, Scolyer RA. Tumours associated with BAP1 mutations. Pathology. 2013;45:116–26.

    CAS  PubMed  Google Scholar 

  230. 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. https://doi.org/10.1186/s12967-015-0485-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  231. 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. Modern Pathol. 2017;30:246–54.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgical Oncology, Fortis SL Raheja Hospital, Mumbai, India

    Ninad Katdare

  2. Department of Surgical Oncology, Zydus Hospital, Ahmedabad, India

    Aditi Bhatt

  3. Department of Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Lyon, France

    Olivier Glehen

Authors
  1. Ninad Katdare
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aditi Bhatt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olivier Glehen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Olivier Glehen .

Editor information

Editors and Affiliations

  1. General and Oncologique Surgery, Centre Hospitalier Lyon-Sud, Lyon, France

    Olivier Glehen

  2. Department of Surgical Oncology, Zydus Hospital, Ahmedabad, India

    Aditi Bhatt

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Katdare, N., Bhatt, A., Glehen, O. (2020). Biomarkers in the Management of Peritoneal Metastases. In: Glehen, O., Bhatt, A. (eds) Pathology of Peritoneal Metastases. Springer, Singapore. https://doi.org/10.1007/978-981-15-3773-8_12

Download citation

  • DOI: https://doi.org/10.1007/978-981-15-3773-8_12

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-15-3772-1

  • Online ISBN: 978-981-15-3773-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation