Malignant Transformation of Endometriosis: Underlying Mechanisms

Although it is well known that ovarian cancer, especially clear cell and endometrioid carcinoma, sometimes develops from endometriotic cyst, the precise mechanism of carcinogenesis is not clarified yet. Recently, several molecules, including HNF-1β, AKT/PI3K/Met, and ARID1A, have been shown to be involved in this carcinogenic process. Some of them are included in the “OCCC signature genes” which we identified as a gene group specifically expressed in clear cell carcinoma among ovarian cancers. “OCCC signature genes” contain many stress-related genes and were induced by treatment with the fluid of endometriotic cysts. The fluid of endometriotic cysts contained significantly high concentration of free iron and oxidative stress-related products. These findings suggest that microenvironment within the endometriotic cyst may play an important role in the malignant transformation of endometriosis and development of clear cell carcinoma, a rare histotype among ovarian cancers. Access this chapter Tax calculation will be finalised at checkout Purchases are for personal use only Similar content being viewed by others

Jimbo H, Hitomi Y, Yoshikawa H, Yano T, Momoeda M, Sakamoto A, Tsutsumi O, Taketani Y, Esumi H. Evidence for monoclonal expansion of epithelial cells in ovarian endometrial cysts. Am J Pathol. 1997;150(4):1173–8. Nilbert M, Pejovic T, Mandahl N, Iosif S, Willén H, Mitelman F. Monoclonal origin of endometriotic cysts. Int J Gynecol Cancer. 1995;5(1):61–3. Tamura M, Fukaya T, Murakami T, Uehara S, Yajima A. Analysis of clonality in human endometriotic cysts based on evaluation of X chromosome inactivation in archival formalin-fixed, paraffin-embedded tissue. Lab Invest. 1998;78(2):213–8. Shin JC, Ross HL, Elias S, Nguyen DD, Mitchell-Leef D, Simpson JL, Bischoff FZ. Detection of chromosomal aneuploidy in endometriosis by multi-color fluorescence in situ hybridization (FISH). Hum Genet. 1997;100(3–4):401–6. Bischoff FZ, Heard M, Simpson JL. Somatic DNA alterations in endometriosis: high frequency of chromosome 17 and p53 loss in late-stage endometriosis. J Reprod Immunol. 2002;55(1–2):49–64. Jiang X, Hitchcock A, Bryan EJ, Watson RH, Englefield P, Thomas EJ, Campbell IG. Microsatellite analysis of endometriosis reveals loss of heterozygosity at candidate ovarian tumor suppressor gene loci. Cancer Res. 1996;56(15):3534–9. Nabeshima H, Murakami T, Yoshinaga K, Sato K, Terada Y, Okamura K. Analysis of the clonality of ectopic glands in peritoneal endometriosis using laser microdissection. Fertil Steril. 2003;80(5):1144–50. Wu Y, Basir Z, Kajdacsy-Balla A, Strawn E, Macias V, Montgomery K, Guo SW. Resolution of clonal origins for endometriotic lesions using laser capture microdissection and the human androgen receptor (HUMARA) assay. Fertil Steril. 2003;79 Suppl 1:710–7. Mayr D, Amann G, Siefert C, Diebold J, Anderegg B. Does endometriosis really have premalignant potential? A clonal analysis of laser-microdissected tissue. FASEB J. 2003;17(6):693–5. Sampson J. Endometrial carcinoma of the ovary, arising in endometrial tissue in that organ. Arch Surg. 1925;10:1–72. Czernobilsky B, Morris WJ. A histologic study of ovarian endometriosis with emphasis on hyperplastic and atypical changes. Obstet Gynecol. 1979;53(3):318–23. LaGrenade A, Silverberg SG. Ovarian tumors associated with atypical endometriosis. Hum Pathol. 1988;19(9):1080–4. Fukunaga M, Nomura K, Ishikawa E, Ushigome S. Ovarian atypical endometriosis: its close association with malignant epithelial tumours. Histopathology. 1997;30(3):249–55. Ogawa S, Kaku T, Amada S, Kobayashi H, Hirakawa T, Ariyoshi K, Kamura T, Nakano H. Ovarian endometriosis associated with ovarian carcinoma: a clinicopathological and immunohistochemical study. Gynecol Oncol. 2000;77(2):298–304. Sáinz de la Cuesta R, Izquierdo M, Cañamero M, Granizo JJ, Manzarbeitia F. Increased prevalence of p53 overexpression from typical endometriosis to atypical endometriosis and ovarian cancer associated with endometriosis. Eur J Obstet Gynecol Reprod Biol. 2004;113(1):87–93. Obata K, Hoshiai H. Common genetic changes between endometriosis and ovarian cancer. Gynecol Obstet Invest. 2000;50 Suppl 1:39–43. Jiang X, Morland SJ, Hitchcock A, Thomas EJ, Campbell IG. Allelotyping of endometriosis with adjacent ovarian carcinoma reveals evidence of a common lineage. Cancer Res. 1998;58(8):1707–12. Prowse AH, Manek S, Varma R, Liu J, Godwin AK, Maher ER, Tomlinson IP, Kennedy SH. Molecular genetic evidence that endometriosis is a precursor of ovarian cancer. Int J Cancer. 2006;119(3):556–62. Goumenou AG, Arvanitis DA, Matalliotakis IM, Koumantakis EE, Spandidos DA. Microsatellite DNA assays reveal an allelic imbalance in p16(Ink4), GALT, p53, and APOA2 loci in patients with endometriosis. Fertil Steril. 2001;75(1):160–5. Sato N, Tsunoda H, Nishida M, Morishita Y, Takimoto Y, Kubo T, Noguchi M. Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary. Cancer Res. 2000;60(24):7052–6. Kato N, Sasou S, Motoyama T. Expression of hepatocyte nuclear factor-1beta (HNF-1beta) in clear cell tumors and endometriosis of the ovary. Mod Pathol. 2006;19(1):83–9. Yamashita Y, Akatsuka S, Shinjo K, Yatabe Y, Kobayashi H, Seko H, Kajiyama H, Kikkawa F, Takahashi T, Toyokuni S. Met is the most frequently amplified gene in endometriosis-associated ovarian clear cell adenocarcinoma and correlates with worsened prognosis. PLoS One. 2013;8(3):e57724. Yamamoto S, Tsuda H, Takano M, Iwaya K, Tamai S, Matsubara O. PIK3CA mutation is an early event in the development of endometriosis-associated ovarian clear cell adenocarcinoma. J Pathol. 2011;225(2):189–94. Jones S, Wang TL, Shih IM, Mao TL, Nakayama K, Roden R, Glas R, Slamon D, Diaz Jr LA, Vogelstein B, Kinzler KW, Velculescu VE, Papadopoulos N. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science. 2010;330(6001):228–31. Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T, Senz J, McConechy MK, Anglesio MS, Kalloger SE, Yang W, Heravi-Moussavi A, Giuliany R, Chow C, Fee J, Zayed A, Prentice L, Melnyk N, Turashvili G, Delaney AD, Madore J, Yip S, McPherson AW, Ha G, Bell L, Fereday S, Tam A, Galletta L, Tonin PN, Provencher D, Miller D, Jones SJ, Moore RA, Morin GB, Oloumi A, Boyd N, Aparicio SA, Shih IM, Mes-Masson AM, Bowtell DD, Hirst M, Gilks B, Marra MA, Huntsman DG. ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med. 2010;363(16):1532–43. Guan B, Wang TL, Shih IM. ARID1A, a factor that promotes formation of SWI/SNF-mediated chromatin remodeling, is a tumor suppressor in gynecologic cancers. Cancer Res. 2011;71(21):6718–27. Katagiri A, Nakayama K, Rahman MT, Rahman M, Katagiri H, Nakayama N, Ishikawa M, Ishibashi T, Iida K, Kobayashi H, Otsuki Y, Nakayama S, Miyazaki K. Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma. Mod Pathol. 2012;25(2):282–8. Yamamoto S, Tsuda H, Takano M, Tamai S, Matsubara O. PIK3CA mutations and loss of ARID1A protein expression are early events in the development of cystic ovarian clear cell adenocarcinoma. Virchows Arch. 2012;460(1):77–87. Lee JC, Son YO, Pratheeshkumar P, Shi X. Oxidative stress and metal carcinogenesis. Free Radic Biol Med. 2012;53(4):742–57. Yamaguchi K, Mandai M, Toyokuni S, Hamanishi J, Higuchi T, Takakura K, Fujii S. Contents of endometriotic cysts, especially the high concentration of free iron, are a possible cause of carcinogenesis in the cysts through the iron-induced persistent oxidative stress. Clin Cancer Res. 2008;14(1):32–40. Körner M, Burckhardt E, Mazzucchelli L. Higher frequency of chromosomal aberrations in ovarian endometriosis compared to extragonadal endometriosis: a possible link to endometrioid adenocarcinoma. Mod Pathol. 2006;19(12):1615–23. Melin A, Sparén P, Persson I, Bergqvist A. Endometriosis and the risk of cancer with special emphasis on ovarian cancer. Hum Reprod. 2006;21(5):1237–42. Yamaguchi K, Mandai M, Oura T, Matsumura N, Hamanishi J, Baba T, Matsui S, Murphy SK, Konishi I. Identification of an ovarian clear cell carcinoma gene signature that reflects inherent disease biology and the carcinogenic processes. Oncogene. 2010;29(12):1741–52. Gonda TA, Tu S, Wang TC. Chronic inflammation, the tumor microenvironment and carcinogenesis. Cell Cycle. 2009;8(13):2005–13. Mandai M, Yamaguchi K, Matsumura N, Baba T, Konishi I. Ovarian cancer in endometriosis: molecular biology, pathology, and clinical management. Int J Clin Oncol. 2009;14(5):383–91. Mandai M, Matsumura N, Baba T, Yamaguchi K, Hamanishi J, Konishi I. Ovarian clear cell carcinoma as a stress-responsive cancer: influence of the microenvironment on the carcinogenesis and cancer phenotype. Cancer Lett. 2011;310(2):129–33. Mabuchi S, Kawase C, Altomare DA, Morishige K, Sawada K, Hayashi M, Tsujimoto M, Yamoto M, Klein-Szanto AJ, Schilder RJ, Ohmichi M, Testa JR, Kimura T. mTOR is a promising therapeutic target both in cisplatin-sensitive and cisplatin-resistant clear cell carcinoma of the ovary. Clin Cancer Res. 2009;15(17):5404–13. Matsumura N, Mandai M, Okamoto T, Yamaguchi K, Yamamura S, Oura T, Baba T, Hamanishi J, Kang HS, Matsui S, Mori S, Murphy SK, Konishi I. Sorafenib efficacy in ovarian clear cell carcinoma revealed by transcriptome profiling. Cancer Sci. 2010;101(12):2658–63. Author information Authors and Affiliations Corresponding author Editor information Editors and Affiliations Rights and permissions Copyright information © 2014 Springer Japan About this chapter Cite this chapter Mandai, M., Yamaguchi, K., Matsumura, N., Konishi, I. (2014). Malignant Transformation of Endometriosis: Underlying Mechanisms. In: Harada, T. (eds) Endometriosis. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54421-0_15 Download citation DOI: https://doi.org/10.1007/978-4-431-54421-0_15 Published: Publisher Name: Springer, Tokyo Print ISBN: 978-4-431-54420-3 Online ISBN: 978-4-431-54421-0 eBook Packages: MedicineMedicine (R0)