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Molecular Biology of Gynaecological Cancers

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Contemporary Obstetrics and Gynecology for Developing Countries

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Abstract

A broad understanding of the molecular abnormalities that underlie gynaecologic malignancies have emerged in the past few years. These molecular changes ultimately drive several hallmarks of cancer including aberrations in growth signals, evasion of apoptosis and immune surveillance, insensitivity to antigrowth signals, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastases. Some of the key molecular aberrations include the DNA damage repair pathway in ovarian cancer, microsatellite instability in endometrial cancer, human papilloma virus-mediated molecular changes in lower genital tract carcinomas, and the role of anti-tumour immunity in all the cancers. This chapter highlights some of the recent molecular findings in gynaecologic malignancies, with an emphasis on clinically applicable developments.

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References

  1. Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004;21:137–48. PMID: 15308095.

    Article  CAS  PubMed  Google Scholar 

  2. Karst AM, Drapkin R. Ovarian cancer pathogenesis: a model in evolution. J Oncol. 2010;2010:932371. PMID: 19746182.

    Article  PubMed  CAS  Google Scholar 

  3. Levanon K, Crum C, Drapkin R. New insights into the pathogenesis of serous ovarian cancer and its clinical impact. J Clin Oncol. 2008;26:5284–93. PMID: 18854563.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Auersperg N, Wong AS, Choi KC, Kang SK, Leung PC. Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr Rev. 2001;22:255–88. PMID: 11294827.

    CAS  PubMed  Google Scholar 

  5. Wright JW, Pejovic T, Fanton J, Stouffer RL. Induction of proliferation in the primate ovarian surface epithelium in vivo. Hum Reprod. 2008;23:129–38. PMID: 18000169.

    Article  CAS  PubMed  Google Scholar 

  6. Wright JW, Pejovic T, Lawson M, Jurevic L, Hobbs T, Stouffer RL. Ovulation in the absence of the ovarian surface epithelium in the primate. Biol Reprod. 2010;82:599–605. PMID: 19923253.

    Article  CAS  PubMed  Google Scholar 

  7. Schlosshauer PW, Cohen CJ, Penault-Llorca F, Miranda CR, Bignon YJ, Dauplat J, Deligdisch L. Prophylactic oophorectomy: a morphologic and immunohistochemical study. Cancer. 2003;98:2599–606. PMID: 14669279.

    Article  PubMed  Google Scholar 

  8. Callahan MJ, Crum CP, Medeiros F, Kindelberger DW, Elvin JA, Garber JE, Feltmate CM, Berkowitz RS, Muto MG. Primary fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction. J Clin Oncol. 2007;25:3985–90. PMID: 17761984.

    Article  PubMed  Google Scholar 

  9. Tone AA, Begley H, Sharma M, Murphy J, Rosen B, Brown TJ, Shaw PA. Gene expression profiles of luteal phase fallopian tube epithelium from BRCA mutation carriers resemble high-grade serous carcinoma. Clin Cancer Res. 2008;14:4067–78. PMID: 18593983.

    Article  CAS  PubMed  Google Scholar 

  10. Kurman RJ. Origin and molecular pathogenesis of ovarian high-grade serous carcinoma. Ann Oncol. 2013;24(Suppl 10):x16–21. PMID: 24265397.

    Article  PubMed  Google Scholar 

  11. Ramus SJ. Current status of inherited predisposition to ovarian cancer: lessons from familial ovarian cancer registries in the UK and USA. In: Odunsi K, Pejovic T, editors. Gynaecologic cancer: a multidisciplinary approach to diagnosis and management. New York: Demos Medical; 2013.

    Google Scholar 

  12. Ramus SJ, Gayther SA. The contribution of BRCA1 and BRCA2 to ovarian cancer. Mol Oncol. 2009;3:138–50. PMID: 19383375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994;266:66–71. PMID: 7545954.

    Article  CAS  PubMed  Google Scholar 

  14. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995;378:789–92. PMID: 8524414.

    Article  CAS  PubMed  Google Scholar 

  15. Mazoyer S. Genomic rearrangements in the BRCA1 and BRCA2 genes. Hum Mutat. 2005;25:415–22. PMID: 15832305.

    Article  CAS  PubMed  Google Scholar 

  16. Antoniou AC, Easton DF. Risk prediction models for familial breast cancer. Future Oncol. 2006;2:257–74. PMID: 16563094.

    Article  PubMed  Google Scholar 

  17. Sakai W, Swisher EM, Karlan BY, Agarwal MK, Higgins J, Friedman C, Villegas E, Jacquemont C, Farrugia DJ, Couch FJ, Urban N, Taniguchi T. Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers. Nature. 2008;451:1116–20. PMID: 18264087.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Walsh T, Lee MK, Casadei S, Thornton AM, Stray SM, Pennil C, Nord AS, Mandell JB, Swisher EM, King MC. Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing. Proc Natl Acad Sci U S A. 2010;107:12629–33. PMID: 20616022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bradford L, Ambrosio A, Birrer MJ. PARP inhibitors in gyecologic malignancies. In: Odunsi K, Pejovic T, editors. Gynaecologic cancers: a multidisciplinary approach to diagnosis and management. New York: Demos Medical; 2013.

    Google Scholar 

  20. Kassim SK, El-Salahy EM, Fayed ST, Helal SA, Helal T, Azzam Eel D, Khalifa A. Vascular endothelial growth factor and interleukin-8 are associated with poor prognosis in epithelial ovarian cancer patients. Clin Biochem. 2004;37:363–9. PMID: 15087251.

    Article  CAS  PubMed  Google Scholar 

  21. Jiang H, Feng Y. Hypoxia-inducible factor 1alpha (HIF-1alpha) correlated with tumour growth and apoptosis in ovarian cancer. Int J Gynecol Cancer. 2006;16(Suppl 1):405–12. PMID: 16515634.

    Article  PubMed  Google Scholar 

  22. Zhu G, Saed GM, Deppe G, Diamond MP, Munkarah AR. Hypoxia up-regulates the effects of prostaglandin E2 on tumour angiogenesis in ovarian cancer cells. Gynecol Oncol. 2004;94:422–6. PMID: 15297183.

    Article  CAS  PubMed  Google Scholar 

  23. Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473–83. PMID: 22204724.

    Article  CAS  PubMed  Google Scholar 

  24. Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G. Intratumoural T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348:203–13. PMID: 12529460.

    Article  CAS  PubMed  Google Scholar 

  25. Smyth MJ, Dunn GP, Schreiber RD. Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumour development and shaping tumour immunogenicity. Adv Immunol. 2006;90:1–50. PMID: 16730260.

    Article  CAS  PubMed  Google Scholar 

  26. Goodell V, Salazar LG, Urban N, Drescher CW, Gray H, Swensen RE, McIntosh MW, Disis ML. Antibody immunity to the p53 oncogenic protein is a prognostic indicator in ovarian cancer. J Clin Oncol. 2006;24:762–8. PMID: 16391298.

    Article  CAS  PubMed  Google Scholar 

  27. Odunsi K, Jungbluth AA, Stockert E, Qian F, Gnjatic S, Tammela J, Intengan M, Beck A, Keitz B, Santiago D, Williamson B, Scanlan MJ, Ritter G, Chen YT, Driscoll D, Sood A, Lele S, Old LJ. NY-ESO-1 and LAGE-1 cancer-testis antigens are potential targets for immunotherapy in epithelial ovarian cancer. Cancer Res. 2003;63:6076–83. PMID: 14522938.

    CAS  PubMed  Google Scholar 

  28. Old LJ. Cancer/testis (CT) antigens – a new link between gametogenesis and cancer. Cancer Immun. 2001;1:1. PMID: 12747762.

    CAS  PubMed  Google Scholar 

  29. Matsuzaki J, Gnjatic S, Mhawech-Fauceglia P, Beck A, Miller A, Tsuji T, Eppolito C, Qian F, Lele S, Shrikant P, Old LJ, Odunsi K. Tumour-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer. Proc Natl Acad Sci U S A. 2010;107:7875–80. PMID: 20385810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Odunsi K, Qian F, Matsuzaki J, Mhawech-Fauceglia P, Andrews C, Hoffman EW, Pan L, Ritter G, Villella J, Thomas B, Rodabaugh K, Lele S, Shrikant P, Old LJ, Gnjatic S. Vaccination with an NY-ESO-1 peptide of HLA class I/II specificities induces integrated humoral and T cell responses in ovarian cancer. Proc Natl Acad Sci U S A. 2007;104:12837–42. PMID: 17652518.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Odunsi K, Matsuzaki J, Karbach J, Neumann A, Mhawech-Fauceglia P, Miller A, Beck A, Morrison CD, Ritter G, Godoy H, Lele S, duPont N, Edwards R, Shrikant P, Old LJ, Gnjatic S, Jager E. Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing NY-ESO-1 antigen in ovarian cancer and melanoma patients. Proc Natl Acad Sci U S A. 2012;109:5797–802. PMID: 22454499.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chiang CL, Kandalaft LE, Tanyi J, Hagemann AR, Motz GT, Svoronos N, Montone K, Mantia-Smaldone GM, Smith L, Nisenbaum HL, Levine BL, Kalos M, Czerniecki BJ, Torigian DA, Powell DJ Jr, Mick R, Coukos G. A dendritic cell vaccine pulsed with autologous hypochlorous acid-oxidized ovarian cancer lysate primes effective broad antitumour immunity: from bench to bedside. Clin Cancer Res. 2013;19:4801–15. PMID: 23838316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kandalaft LE, Chiang CL, Tanyi J, Motz G, Balint K, Mick R, Coukos G. A phase I vaccine trial using dendritic cells pulsed with autologous oxidized lysate for recurrent ovarian cancer. J Transl Med. 2013;11:149. PMID: 23777306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Tsuji T, Matsuzaki J, Kelly MP, et al. “Antibody-targeted NYESO-1 to mannose receptor or DEC-205 in vitro elicits dual human CD8+ and CD4+ T cell responses with broad antigen Journal of Drug Delivery 17 specificity”, J. Immunol. 2011;186(2):1218–27.

    Google Scholar 

  35. van Rooij N, van Buuren MM, Philips D, Velds A, Toebes M, Heemskerk B, et al. Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma. J Clin Oncol. 2013;31:e439–42. https://doi.org/10.1200/jco.2012.47.7521.

  36. Disis ML, Patel MR, Pant S, et al. Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with previously treated, recurrent or refractory ovarian cancer: A phase Ib, open-label expansion trial. J Clin Oncol. 2015;33:5509–81.

    Article  Google Scholar 

  37. Snyder A, Makarov V, Merghoub T, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371:2189–99.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Mutter GL, Boynton KA, Faquin WC, Ruiz RE, Jovanovic AS. Allelotype mapping of unstable microsatellites establishes direct lineage continuity between endometrial precancers and cancer. Cancer Res. 1996;56:4483–6. PMID: 8813144.

    CAS  PubMed  Google Scholar 

  39. Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Baak JP, Lees JA, Weng LP, Eng C. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst. 2000;92:924–30. PMID: 10841828.

    Article  CAS  PubMed  Google Scholar 

  40. Caduff RF, Johnston CM, Frank TS. Mutations of the Ki-ras oncogene in carcinoma of the endometrium. Am J Pathol. 1995;146:182–8. PMID:7856726.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Mirabelli-Primdahl L, Gryfe R, Kim H, Millar A, Luceri C, Dale D, Holowaty E, Bapat B, Gallinger S, Redston M. Beta-catenin mutations are specific for colorectal carcinomas with microsatellite instability but occur in endometrial carcinomas irrespective of mutator pathway. Cancer Res. 1999;59:3346–51. PMID: 10416591.

    CAS  PubMed  Google Scholar 

  42. Busmanis I, Ho TH, Tan SB, Khoo KS. p53 and bcl-2 expression in invasive and pre-invasive uterine papillary serous carcinoma and atrophic endometrium. Ann Acad Med Singap. 2005;34:421–5. PMID: 16123814.

    CAS  PubMed  Google Scholar 

  43. zur Hausen H. Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst. 2000;92:690–8. PMID:10793105.

    Google Scholar 

  44. Shope RE. Serial transmission of vrus of infectious paillomatosis in domestic rabbits. Proc Soc Exp Biol Med. 1935;32:830.

    Article  Google Scholar 

  45. Wentzensen N, Vinokurova S, von Knebel Doeberitz M. Systematic review of genomic integration sites of human papillomavirus genomes in epithelial dysplasia and invasive cancer of the female lower genital tract. Cancer Res. 2004;64:3878–84. PMID: 15172997.

    Article  CAS  PubMed  Google Scholar 

  46. Duensing S, Munger K. Centrosome abnormalities, genomic instability and carcinogenic progression. Biochim Biophys Acta. 2001;1471:M81–8. PMID: 11342187.

    CAS  PubMed  Google Scholar 

  47. Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med. 1998;338:423–8. PMID: 9459645.

    Article  CAS  PubMed  Google Scholar 

  48. Zhou J, Liu WJ, Peng SW, Sun XY, Frazer I. Papillomavirus capsid protein expression level depends on the match between codon usage and tRNA availability. J Virol. 1999;73:4972–82. PMID: 10233959.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Koutsky LA, Ault KA, Wheeler CM, Brown DR, Barr E, Alvarez FB, Chiacchierini LM, Jansen KU. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med. 2002;347:1645–51. PMID: 12444178.

    Article  CAS  PubMed  Google Scholar 

  50. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189:12–9. PMID: 10451482.

    Article  CAS  PubMed  Google Scholar 

  51. Crum CP. The beginning of the end for cervical cancer? N Engl J Med. 2002;347:1703–5. PMID: 12444186.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Oregon Health and Science University, Portland, OR, USA

    Tanja Pejovic

  2. Roswell Park Comprehensive Cancer Centre (Roswell Park), Buffalo, NY, USA

    Kunle Odunsi

  3. Department of Gynaecologic Oncology, Centre for Immunotherapy, Roswell Park, Buffalo, NY, USA

    Kunle Odunsi

  4. University of Buffalo, Buffalo, NY, USA

    Kunle Odunsi

Authors
  1. Tanja Pejovic
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  2. Kunle Odunsi
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Correspondence to Kunle Odunsi .

Editor information

Editors and Affiliations

  1. Centre of Excellence in Reproductive Health Innovation, Department of Obstetrics and Gynaecology, University of Benin, Benin City, Nigeria

    Friday Okonofua

  2. College of Health Sciences, Chicago State University, Chicago, IL, USA

    Joseph A. Balogun

  3. Roswell Park Cancer Institute, Buffalo, NY, USA

    Kunle Odunsi

  4. Clinical Obstetrics and Gynaecology, Weil Cornell Medicine, Doha, Qatar

    Victor N. Chilaka

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Pejovic, T., Odunsi, K. (2021). Molecular Biology of Gynaecological Cancers. In: Okonofua, F., Balogun, J.A., Odunsi, K., Chilaka, V.N. (eds) Contemporary Obstetrics and Gynecology for Developing Countries . Springer, Cham. https://doi.org/10.1007/978-3-030-75385-6_53

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  • DOI: https://doi.org/10.1007/978-3-030-75385-6_53

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