Concurrent Endometrial Intraepithelial Carcinoma (EIC) and Serous Ovarian Cancer: Can EIC Be Seen as the Precursor Lesion?

Abstract

This study provides a first indication of EIC as possible precursor lesion for SOC. This finding could have major clinical implications for future ovarian cancer management and underscores EIC as a possible target for early SOC detection and prevention.

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

“…24,26,36 TP53-mutation analysis well defines the cellular lineage between primary organ sites and potential metastasis including serous endometrial intraepithelial carcinoma and associated extrauterine disease. 16,20,22,27,46 In 10 of the 21 serous endometrial intraepithelial carcinoma cases, multiple TP53 gene mutations were identified and identical mutations were found between the foci of serous endometrial intraepithelial carcinoma and their associated extrauterine disease, supporting that the extrauterine disease represents metastasis from corresponding serous endometrial intraepithelial carcinomas. In contrast, 5 of the 21 serous endometrial intraepithelial carcinoma cases showed discordant TP53 mutations between intrauterine and extrauterine samples, suggesting that associated extrauterine disease in those samples was not derived from the metastatic serous endometrial intraepithelial carcinoma but rather from the tubal origin.…”

“…[41][42][43] Pelvic serous carcinoma, in the presence of endometrial serous carcinoma, particularly serous endometrial intraepithelial carcinoma, is equivalent to serous endometrial intraepithelial carcinoma associated with extrauterine disease. 16 Identifying the cellular source for extrauterine disease associated with serous endometrial intraepithelial carcinoma as well as the cell of origin may benefit patient care.…”

“…TP53 is the most commonly altered tumor suppressor gene in human malignancies to date. 16,44 Approximately 90% of TP53 mutations occur in exons 5-8. 44 TP53 alteration has a key role in endometrial serous carcinoma carcinogenesis.…”

“…Transtubal cancer spread has been demonstrated previously. 16,20,21,39 This may explain the high incidence of extrauterine disease in serous endometrial intraepithelial carcinoma cases, although the detailed molecular mechanisms remain to be clarified.…”

“…15 Alternative hypotheses include synchronous endometrial and adnexal origins as well as singular adnexal origin for both serous endometrial intraepithelial carcinoma and extrauterine disease. [16][17][18][19][20][21][22][23] Identifying the cell of origin of extrauterine disease in patients with serous endometrial intraepithelial carcinoma may improve cancer detection, prevention, management, and optimally reduce the mortality of this fatal disease.…”