Primary sources of pelvic serous cancer in patients with endometrial intraepithelial carcinoma

Abstract

Serous endometrial intraepithelial carcinoma is often associated with extrauterine disease. It is currently unclear where does the extrauterine disease come from. This study addressed this issue. A total of 135 samples from 21 serous endometrial intraepithelial carcinoma patients were studied. Cellular lineage relationships between intrauterine and extrauterine serous carcinomas were determined by TP53-mutation analysis and correlated to the clinicopathologic features. There were three conditions contributing the extrauterine disease: metastasis from serous endometrial intraepithelial carcinoma (n ¼ 10) showed identical TP53 mutation between intrauterine lesions and extrauterine disease, cases of adnexal origin (n ¼ 5) had discordant TP53 mutations, and the mixed cellular origin cases (n ¼ 6) with both identical and discordant mutation status. Patients with extrauterine disease from serous endometrial intraepithelial carcinoma metastasis typically had small tumor masses (o2 cm) in extrauterine sites and without finding of serous tubal intraepithelial carcinoma, while extrauterine disease with adnexal or tubal origin commonly had larger tumor masses in extrauterine sites including ovary and omentum and serous tubal intraepithelial carcinoma. The majority of extrauterine diseases associated with serous endometrial intraepithelial carcinoma are metastasized from the endometrium. Serous endometrial intraepithelial carcinoma is frequently associated with serous cancers of adnexal or tubal origin, indicating that endometrial and adnexal or tubal serous cancers may share similar etiologies. TP53-mutation analysis provides a strong linkage for cellular lineage analysis. Tumor size in extrauterine disease and presence of serous tubal intraepithelial carcinoma or not are useful clinicopathologic features to determine primary cancer site, which helps in clinical management.

Association between tubal ligation and endometrial cancer risk: A Swedish population‐based cohort study

“…However, the origin of serous pelvic carcinomas is debated and a monoclonal origin was suggested >20 years ago . Mutation analysis of coexisting tubal and endometrial serous disease suggest that a subset of USC arise in the fallopian tubes . This is further supported by our analysis of tumor morphology, showing that the association was most pronounced for non‐endometrioid tumors.…”

Relationships of Tubal Ligation to Endometrial Carcinoma Stage and Mortality in the NRG Oncology/Gynecologic Oncology Group 210 Trial

“…Further, molecular analysis in these cases suggests that intraand extra-uterine tumor cells are often clonally related (18)(19)(20)(21). Among 21 endometrial intraepithelial carcinomas associated with concurrent extra-uterine tumor deposits, Jia et al (18) found identical p53 mutations across foci in 10 cases and overlapping patterns in six cases. None of the 10 cases with identical mutations were found to contain serous tubal intraepithelial carcinomas, but three contained tumor cells in the tubal lumen.…”

“…Notably, "minimal uterine serous carcinoma" (15), which comprises approximately 20% of serous tumors (14,16), has been found to present with extra-uterine disease in up to 45% of women (17). Further, molecular analysis in these cases suggests that intraand extra-uterine tumor cells are often clonally related (18)(19)(20)(21). Among 21 endometrial intraepithelial carcinomas associated with concurrent extra-uterine tumor deposits, Jia et al (18) found identical p53 mutations across foci in 10 cases and overlapping patterns in six cases.…”

Serous Endometrial Intraepithelial Carcinoma Involving Endometrial Polyp Diagnosed by Transcervical Resection: A Case Report

“…P53 alteration is a molecular signature of serous endometrial carcinoma. P53 mutational analysis is reported to be a useful tool to detect the primary source of extrauterine metastatic lesions of the serous intraepithelial carcinoma [16]. Additional molecular events might to be involved in carcinogenesis of serous endometrial carcinogenesis, even in endometrial intraepithelial carcinoma.…”