Synchronous primary endometrial and ovarian cancers: how to diagnose, differentiate and treat in the light of recent available literature data
Susan Afshari-Stasiak 1 , Jacek Wilczyński 1 , Maria Szubert 1Abstract
SEO – synchronous endometrial ovarian cancer is a well-known phenomenon, which has for years been managed as two primary independent cancers. The results of recent molecular studies, especially next-generation sequencing, suggest that the condition should be regarded as a continuum, with its origin probably lying in the endometrium or endometrial foci. It has been found that 0.7% to 1.0% of endometriosis patients may develop malignant lesions. Although SEO is being increasingly studied, diagnostics and treatment still leave many questions. The most important thing is to improve the diagnosis with rapid and simple detection. A few molecular methods are already known, but genetic diagnostic, still remains unclear. Old criteria implemented by Scully in 1998 should be nowadays complemented by immunohistochemical staining of estrogen and progestin receptors, bcl2 antibodies and molecular analyses of genes: B-catenin, PTEN, KRAS, TP53, PIK3CA and microsatellite instability. Will genetic diagnostics preserve fertility in young patients with SEO? This paper reviews relevant literature to determine a strategy for distinguishing between SEO and metastatic cancers, and presents management options for patients with SEO.
References
- 1. AlHilli M.M., Dowdy S.C., Weaver A.L., St Sauver J.L., Keeney G.L.,Mariani A., Podratz K.C., Bakkum-Gamez J.N.: Incidence and factorsassociated with synchronous ovarian and endometrial cancer: A population-based case-control study. Gynecol. Oncol., 2012; 125: 109–113 2 Anglesio M.S., Wang Y.K., Maassen M., Horlings H.M., BashashatiA., Senz J., Mackenzie R., Grewal D.S., Li-Chang H., Karnezis A.N.,Sheffield B.S., McConechy M.K., Kommoss F., Taran F.A., Staebler A.,et al.: Synchronous endometrial and ovarian carcinomas: Evidenceof clonality. J. Natl. Cancer Inst., 2016; 108: djv428 3 Bese T., Sal V., Kahramanoglu I., Tokgozoglu N., Demirkiran F.,Turan H., Ilvan S., Arvas M.: Synchronous primary cancers of theendometrium and ovary with the same histopathologic type versusendometrial cancer with ovarian metastasis: A single institution reviewof 72 cases. Int. J. Gynecol. Cancer, 2016; 26: 394–406
Google Scholar - 2. in epithelial ovarian cancer: A meta-analysis of observationalstudies. Gynecol. Oncol., 2013; 129: 613–619
Google Scholar - 3. mutations of CTNNB1 drive tumorigenesis: A review. Oncotarget,2017; 9: 5492–5508
Google Scholar - 4. Brinkmann D., Ryan A., Ayhan A., McCluggage W.G., Feakins R.,Santibanez-Koref M.F., Mein C.A., Gayther S.A., Jacobs I.J.: A moleculargenetic and statistical approach for the diagnosis of dual-sitecancers. J. Nat. Cancer Inst., 2004; 96: 1441–1446
Google Scholar - 5. Burleigh A., Talhouk A., Gilks C.B., McAlpine J.N.: Clinical andpathological characterization of endometrial cancer in young women:Identification of a cohort without classical risk factors. GynecolOncol., 2015; 138: 141–146
Google Scholar - 6. Cancer Genome Atlas Research Network, Kandoth C., Schultz N.,Cherniack A.D., 9Akbani R., Liu Y., Shen H., Robertson A.G., PashtanI., Shen R., Benz C.C., Yau C., Laird P.W., Ding L., Zhang W., Mills G.B.,Kucherlapati R., Mardis E.R., Levine D.A.: Integrated genomic characterizationof endometrial carcinoma. Nature, 2013; 497: 67–73
Google Scholar - 7. Chan J.L., Wang E.T.: Oncofertility for women with gynecologicmalignancies. Gynecol. Oncol., 2017; 144: 631–636
Google Scholar - 8. Chen L., Zhao Q., Lv X.: Characteristics and prognosis of coexistingadnexa malignancy with endometrial cancer: A single institutionreview of 51 cases. Arch. Gynecol. Obstet., 2011; 283: 1133–1137
Google Scholar - 9. Colombo N., Creutzberg C., Amant F., Bosse T., González-MartínA., Ledermann J., Marth C., Nout R., Querleu D., Mirza M.R., SessaC., ESMO-ESGO-ESTRO Endometrial Consensus Conference WorkingGroup: ESMO-ESGO-ESTRO consensus conference on endometrialcancer: Diagnosis, treatment and follow-up. Ann. Oncol., 2016;27: 16–41
Google Scholar - 10. Colombo N., Preti E., Landoni F., Carinelli S., Colombo A., MariniC., Sessa C., ESMO Guidelines Working Group.: Endometrial cancer:ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol., 2013; 24: vi33–vi38
Google Scholar - 11. Cunliffe W.J., Hasleton P.S., Tweedle D.E., Schofield P.F.: Incidenceof synchronous and metachronous colorectal carcinoma.Br. J. Surg., 1984; 71: 941–943
Google Scholar - 12. Dębska-Szmich S., Czernek U., Krakowska M., Frąckowiak M.,Zięba A., Czyżykowski R., Kulejewska D., Potemski P.: Synchronousprimary ovarian and endometrial cancers: A series of cases anda review of literature. Prz. Menopauzalny, 2014; 13: 64–69
Google Scholar - 13. Dogan A., Schultheis B., Rezniczek G.A., Hilal Z., Cetin C., HäuslerG., Tempfer C.B.: Synchronous endometrial and ovarian cancerin young women: Case report and review of the literature. AnticancerRes., 2017; 37: 969–978
Google Scholar - 14. Fagotti A., Ferrandina G., Fanfani F., Legge F., Lauriola L., GessiM., Castelli P., Barbieri F., Minelli L., Scambia G.: Analysis of cyclooxygenase- 2 (COX-2) expression in different sites of endometriosisand correlation with clinico-pathological parameters. Hum.Reprod., 2004; 19: 393–397
Google Scholar - 15. Fujii H., Matsumoto T., Yoshida M., Furugen Y., Takagaki T.,Iwabuchi K., Nakata Y., Takagi Y., Moriya T., Ohtsuji N., Ohtsuji M.,Hirose S., Shirai T.: Genetics of synchronous uterine and ovarianendometrioid carcinoma: Combined analyses of loss of heterozygosity,PTEN mutation, and microsatellite instability. Hum. Pathol.,2002; 33: 421–428
Google Scholar - 16. Gao C., Wang Y., Broaddus R., Sun L., Xue F., Zhang W.: Exon
Google Scholar - 17. Garavaglia E., Sigismondi C., Ferrari S., Candiani M.: The originof endometriosis-associated ovarian cancer from uterine neoplasticlesions. Med. Hypotheses, 2018; 110: 80–82
Google Scholar - 18. Gilks B.C., Singh N.: Synchronous carcinomas of endometriumand ovary: A pragmatic approach. Gynecol. Oncol. Rep., 2018;27: 72–73
Google Scholar - 19. Goyal A., Masand R.P., Roma A.A.: Value of PAX-8 and SF-1 immunohistochemistryin the distinction between female adnexaltumor of probable wolffian origin and its mimics. Int. J. Gynecol.Pathol., 2016; 35: 167–175
Google Scholar - 20. Guerra F., Girolimetti G., Perrone A.M., Procaccini M., KurelacI., Ceccarelli C., De Biase D., Caprara G., Zamagni C., De Iaco P., SantiniD., Gasparre G.: Mitochondrial DNA genotyping efficiently revealsclonality of synchronous endometrial and ovarian cancers.Mod. Pathol., 2014; 27: 1412–1420
Google Scholar - 21. Hájková N, Tichá I., Hojný J., Němejcová K., Bártů M., MichálkováR., Zikán M., Cibula D., Laco J., Geryk T., Méhes G., Dundr P.:Synchronous endometrioid endometrial and ovarian carcinomasare biologically related: A clinico‐pathological and molecular (nextgeneration sequencing) study of 22 cases. Oncol. Lett., 2019; 17:2207–2214
Google Scholar - 22. Heitz F., Amant F., Fotopoulou C., Battista M.J., Wimberger P.,Traut A., Fisseler-Eckhoff A., Harter P., Vandenput I., Sehouli J.,Schmidt M., Kimmig R., du Bois R., du Bois A.: Synchronous ovarianand endometrial cancer – an international multicenter casecontrolstudy. Int. J. Gynecol. Cancer, 2014; 24: 54–60
Google Scholar - 23. Hui P.,Gysler S.M., Uduman M., Togun T.A., Prado D.E., BrambsC.E., Nallur S., Schwartz P.E., Rutherford T.J., Santin A.D., WeidhaasJ.B., Ratner E.S.: MicroRNA signatures discriminate between uterineand ovarian serous carcinomas. Hum. Pathol., 2018; 76: 133–140
Google Scholar - 24. Irving J.A., Catasús L., Gallardo A., Bussaglia E., Romero M.,Matias-Guiu X., Prat J.: Synchronous endometrioid carcinomas ofthe uterine corpus and ovary: Alterations in the β-catenin (CTNNB1)pathway are associated with independent primary tumorsand favorable prognosis. Hum. Pathol., 2005; 36: 605–619
Google Scholar - 25. Kaneki E., Oda Y., Ohishi Y., Tamiya S., Oda S., Hirakawa T.,Nakano H., Tsuneyoshi M.: Frequent microsatellite instability insynchronous ovarian and endometrial adenocarcinoma and its usefulnessfor differential diagnosis. Hum. Pathol., 2004; 35: 1484–1493
Google Scholar - 26. Kelemen L.E., Rambau P.F., Koziak J.M., Steed H., Köbel M.:Synchronous endometrial and ovarian carcinomas: Predictors ofrisk and associations with survival and tumor expression profiles.Cancer Causes Control, 2017; 28: 447–457
Google Scholar - 27. Kobayashi Y., Nakamura K., Nomura H, Banno K., Irie H., AdachiM., Iida M., Umene K., Nogami Y., Masuda K., Kisu I., Ueki A., YamagamiW., Kataoka F., Hirasawa A., et.al.: Clinicopathologic analysiswith immunohistochemistry for DNA mismatch repair protein expressionin synchronous primary endometrial and ovarian cancers.Int. J. Gynecol. Cancer, 2015; 25: 440–446
Google Scholar - 28. Ledermann J.A., Raja F.A., Fotopoulou C., Gonzalez-Martin A.,Colombo N., Sessa C.: Newly diagnosed and relapsed epithelialovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis,treatment and follow-up. Ann. Oncol., 2013; 24: vi24-vi32
Google Scholar - 29. Lee J.Y., Myung S.K., Song Y.S.: Prognostic role of cyclooxygenase-
Google Scholar - 30. Lin K.Y., Miller D.S., Bailey A.A., Andrews S.J., Kehoe S.M.,Richardson D.L., Lea J.S.: Ovarian involvement in endometrioidadenocarcinoma of uterus. Gynecol. Oncol., 2015; 138: 532–535
Google Scholar - 31. Lin W.M., Forgacs E., Warshal D.P., Yeh I.T., Martin J.S., AshfaqR., Muller C.Y.: Loss of heterozygosity and mutation analysis ofthe PTEN/MMAC1 gene in synchronous endometrial and ovariancarcinomas. Clin. Cancer Res., 1998; 4: 2577–2583
Google Scholar - 32. Maggi R., Lissoni A., Spina F., Melpignano M., Zola P., FavalliG., Colombo A., Fossati R.: Adjuvant chemotherapy vs radiotherapyin high-risk endometrial carcinoma: Results of a randomised trial.Br. J. Cancer, 2006; 95: 266–271
Google Scholar - 33. Matsuo K., Machida H., Blake E.A., Holman L.L., Rimel B.J.,Roman L.D., Wright J.D.: Trends and outcomes of women withsynchronous endometrial and ovarian cancer. Oncotarget, 2018;9: 28757–28771
Google Scholar - 34. Moro F., Leombroni M., Pasciuto T., Trivellizzi I.N., MasciliniF., Ciccarone F., Zannoni G.F., Fanfani F., Scambia G., Testa A.C.:Synchronous primary cancers of endometrium and ovary vs endometrialcancer with ovarian metastasis: An observational study.Ultrasound Obstet. Gynecol., 2019; 53: 827–835
Google Scholar - 35. Møller P., Seppälä T., Bernstein I., Holinski-Feder E., Sala P.,Evans D.G., Lindblom A., Macrae F., Blanco I., Sijmons R., JeffriesJ., Vasen H., Burn J., Nakken S., Hovig E., et al.: Cancer incidenceand survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: First report from the prospectiveLynch syndrome database. Gut, 2017; 66: 464–472
Google Scholar - 36. Perrone A.M., Girolimetti G., Procaccini M., Marchio L., LiviA., Borghese G., Porcelli A.M., De Iaco P., Gasparre G.: Potential formitochondrial DNA sequencing in the differential diagnosis of gynaecologicalmalignancies. Int. J. Mol. Sci., 2018; 19: 2048
Google Scholar - 37. Rodolakis A., Thomakos N., Akrivos N., Sotiropoulou M., IoannidisI., Haidopoulos D., Vlachos G., Antsaklis A.: Clinicopathologicinsight of simultaneously detected primary endometrial and ovariancarcinomas. Arch. Gynecol. Obstet., 2012; 285: 817–821
Google Scholar - 38. Schultheis A.M., Ng C.K., De Filippo M.R., Piscuoglio S., MacedoG.S., Gatius S., Perez Mies B., Soslow R.A., Lim R.S., Viale A., HubermanK.H., Palacios J.C., Reis-Filho J.S., Matias-Guiu X., Weigelt B.:Massively parallel sequencing-based clonality analysis of synchronousendometrioid endometrial and ovarian carcinomas. J. Natl.Cancer Inst., 2016; 108: djv427
Google Scholar - 39. Scully R.E., Young R.H., Clement P.B.: Tumors of the ovary,maldeveloped gonads, fallopian tube and broad ligament; ArmedForces Institute of Pathology. Washington DC 1998, 126–127
Google Scholar - 40. Soliman P.T., Broaddus R.R., Schmeler K.M., Daniels M.S., GonzalezD., Slomovitz B.M., Gershenson D.M., Lu K.H.: Women withsynchronous primary cancers of the endometrium and ovary: Dothey have Lynch syndrome? J. Clin. Oncol., 2005; 23: 9344–9350
Google Scholar - 41. Soliman P.T., Slomovitz B.M., Broaddus R.R., Sun C.C., Oh J.C.,Eifel P.J., Gershenson D.M., Lu K.H.: Synchronous primary cancersof the endometrium and ovary: A single institution review of 84cases. Gynecol. Oncol., 2004; 94: 456–462
Google Scholar - 42. Solmaz U., Karatasli V., Mat E., Dereli L., Hasdemir P.S., EkinA., Gezer C., Sayhan S., Sanci M., Guvenal T.: Synchronous primaryendometrial and ovarian cancers: A multicenter review of 63 cases.Tumori, 2016; 102: 508–513
Google Scholar - 43. Song T., Seong S.J., Bae D.S., Suh D.H., Kim D.Y., Lee K.H., LimM.C., Lee T.S.: Synchronous primary cancers of the endometriumand ovary in young women:A Korean Gynecologic Oncology GroupStudy. Gynecol Oncol., 2013; 131: 624–628
Google Scholar - 44. Stewart C.J., Crum C.P., McCluggage W.G., Park K.J., RutgersJ.K., Oliva E., Malpica A., Parkash V., Matias-Guiu X., Ronnett B.M.:Guidelines to aid in the distinction of endometrial and endocervicalcarcinomas, and the distinction of independent primary carcinomasof the endometrium and adnexa from metastatic spreadbetween these and other sites. Int. J. Gynecol. Pathol., 2019; 38:S75–S92
Google Scholar - 45. Suda K., Nakaoka H., Yoshihara K., Ishiguro T., Tamura R., MoriY., Yamawaki K., Adachi S., Takahashi T., Kase H., Tanaka K., YamamotoT., Motoyama T., Inoue I., Enomoto T.: Clonal expansion anddiversification of cancer-associated mutations in endometriosisand normal endometrium. Cell Rep., 2018; 24: 1777–1789
Google Scholar - 46. Szubert M., Suzin J., Obirek K., Sochacka A., Łoszakiewicz M.:Clear cell ovarian cancer and endometriosis: Is there a relationship?Prz. Menopauzalny, 2016; 15: 85–89
Google Scholar - 47. Tong S.Y., Lee Y.S., Park J.S., Bae S.N., Lee J.M., NamkoongS.E.: Clinical analysis of synchronous primary neoplasms of thefemale reproductive tract. Eur. J. Obstet. Gynecol. Reprod. Biol.,2008; 136: 78–82
Google Scholar - 48. Turashvili G., Gómez-Hidalgo N.R., Flynn J., Gonen M., LeitaoM.M. Jr, Soslow R.A., Murali R.: Risk-based stratification of carcinomasconcurrently involving the endometrium and ovary. Gynecol.Oncol., 2019; 152: 38–45
Google Scholar - 49. Tziris N., Dokmetzioglou J., Giannoulis K., Kesisoglou I., SapalidisK., Kotidis E., Gambros O.: Synchronous and metachronous adenocarcinomasof the large intestine. Hippokratia, 2008; 12: 150–152
Google Scholar - 50. Vercellini P., Viganò P., Somigliana E., Fedele L.: Endometriosis:Pathogenesis and treatment. Nat. Rev. Endocrinol., 2014; 10:261–275
Google Scholar - 51. Wang C.J., Christie A., Folkert M.R., Xie X.J., Albuquerque K.:Value of combined adjuvant chemotherapy and radiation on survivalfor stage III uterine cancer: Is less radiation equal to more?J. Gynecol. Oncol., 2018; 29: e49
Google Scholar - 52. Wang T., Zhang X., Lu Z., Wang J., Hua K.: Comparison andanalysis of the clinicopathological features of SCEO and ECOM.J. Ovarian Res., 2019; 12: 10
Google Scholar - 53. Wilson M.R., Reske J.J., Holladay J., Wilber G.E., Rhodes M., KoemanJ., Adams M., Johnson B., Su R.W., Joshi N.R., Patterson A.L.,Shen H., Leach R.E., Teixeira J.M., et al.: ARID1A and PI3-kinasepathway mutations in the endometrium drive epithelial transdifferentiationand collective invasion. Nat. Commun., 2019; 10: 3554
Google Scholar - 54. Wu R.C., Veras E., Lin J., Gerry E., Bahadirli-Talbott A., BarasA., Ayhan A., Shih I.M., Wang T.L.: Elucidating the pathogenesis of synchronous and metachronous tumors in a woman with endometrioidcarcinomas using a whole-exome sequencing approach.Cold Spring Harb. Mol Case Stud., 2017; 3, a001693
Google Scholar - 55. Yang L., Zhang L., Huang Q., Liu C., Qi L., Li L., Qu T., Wang Y.,Liu S., Meng B., Sun B., Cao W.: Combination of scoring criteria andwhole exome sequencing analysis of synchronous endometrialand ovarian carcinomas. Int. J. Gynecol. Cancer, 2018; 28: 704–712
Google Scholar - 56. Zhan X., Li L., Wu M., Lang J.: The prognosis of stage IA synchronousendometrial endometrioid and ovarian carcinomas. Arch.Gynecol. Obstet., 2019; 300: 1045–1052
Google Scholar