Synchronous Endometrial and Ovarian Carcinomas: Evidence of Clonality

Abstract

Many women with ovarian endometrioid carcinoma present with concurrent endometrial carcinoma. Organ-confined and low-grade synchronous endometrial and ovarian tumors (SEOs) clinically behave as independent primary tumors rather than a single advanced-stage carcinoma. We used 18 SEOs to investigate the ancestral relationship between the endometrial and ovarian components. Based on both targeted and exome sequencing, 17 of 18 patient cases of simultaneous cancer of the endometrium and ovary from our series showed evidence of a clonal relationship, ie, primary tumor and metastasis. Eleven patient cases fulfilled clinicopathological criteria that would lead to classification as independent endometrial and ovarian primary carcinomas, including being of FIGO stage T1a/1A, with organ-restricted growth and without surface involvement; 10 of 11 of these cases showed evidence of clonality. Our observations suggest that the disseminating cells amongst SEOs are restricted to physically accessible and microenvironment-compatible sites yet remain indolent, without the capacity for further dissemination.

Synchronous Endometrial and Ovarian Cancer in Young Women: Case Report and Review of the Literature

“…Our analysis confirms that the majority of SEOC cases are diagnosed at an early stage and display synchronous endometrioid adenocarcinomas in both endometrium and ovary. Specifically, we found that 72% of EC cases and 70% of ovarian cancer cases were classified as FIGO stage I (13). Others have confirmed these findings by subjecting cancer tissue from five SEOC cases to whole-exome massively parallel sequencing, demonstrating that the endometrial and ovarian tumor cells displayed strikingly similar repertoires of somatic mutations and gene copy number alterations in all investigated cases (14).…”

“…In addition to these favorable clinicapthologic characteristics, the prognosis of women with SEOC seems to be better than that of women with single ovarian cancer, independent of tumor stage (5). This may be due to genetically-based restrictions of tumor dissemination in women with SEOC (13). In our analysis of survival data in the literature, the mean recurrence-free survival time of young women with SEOC was 1.9 years and the mean overall survival time was 4.0 years.…”

“…The bulk of studies identified in this systematic review were retrospective cohort studies with <50 patients with SEOC (6-10, 12, 22, 24, 25, 28, 31, 34, 37, 38, 42, 44, 49, 51, 52, 55, 56, 58, 59, 61, 62, 65, 67-71), cases series of individual patients (13,23,35,36,43,45,66,73), and case reports (26,27,32,33,41,46,50,53,54,57,60,63,64,72,74,75). As expected, the heterogeneity among these studies with low numbers of patients was high.…”

“…the endometrium and the ovary, with a limited capacity for further dissemination (13). Others have confirmed a high rate of monoclonality among SEOC cases (14).…”

Vaginal hysterectomy with or without bilateral salpingo-oophorectomy may be an alternative treatment for endometrial cancer patients with medical co-morbidities precluding standard surgical procedures: a systematic review

“…It would be interesting to determine whether post-menopausal patients would also have a less favorable prognosis. Most synchronous ovarian cancers were found to be clonally related to endometrial carcinomas, suggesting the possibility of a metastatic event 26. More importantly, these patients had a favorable prognosis, suggesting that the disseminating cells are restricted to physically accessible and microenvironmentally compatible sites, yet remain indolent without the capacity for further dissemination.…”