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.
Background: Almost half of ovarian endometrioid histotype carcinomas present with concurrent endometrial carcinoma or pre-cancerous lesions. These “synchronous” ovarian and endometrial (SEO) tumors, when organ-confined and low-grade, consistently behave as two independent primary tumors, rather than a tumor-metastasis pair typical of advanced-stage carcinoma. Our study aims to investigate the ancestral relationship between ovarian and endometrial components of SEOs. Methods: We identified a cohort of SEOs and performed targeted, with the Illumina Truseq Custom Amplicon assay, and exome-level, with Nugen Ovation Library System and Agilent SureSelect XT2 capture, library construction followed by massively parallel sequencing on illumina MiSeq or HiSeq. Results: Despite complexities introduced as a result of sampling formalin fixed and paraffin embedded archival specimens we were able to confirm shared identical mutations, and thus a clonal relationship, between ovarian and endometrial tumors in all but one case. Discussion: In simultaneous presentation of cancer of the endometrium and ovary from our series we observed strong evidence of a primary tumor and metastasis relationship. However, the clinical behavior of this series, and SEOs in general, defies the basic tenant of cancer metastasis as a dire prognosis. Curiously similar anomalies, where there is advanced stage yet favorable outcome, occur in other organ systems. We therefore suggest a generalizable process “pseudo-metastasis” through which cells can spread to microenvironment-compatible and physically accessible sites. This restricted metastatic process can occur in cells that lack the full complement of cancer-associated transformation hallmarks required for tissue invasion and hematogenous or lymphatic metastasis. This phenomenon may be an important early step in dissemination of apparent multi-focal benign lesions, pre-malignant lesions, and low-grade carcinomas. This abstract is also presented as Poster B07. Citation Format: Michael S. Anglesio, Yi Kan Wang, Madlen Maassen, Hugo M. Horlings, Ali Bashashati, Blake Gilks, Stefan Kommoss, David G. Huntsman. Synchronous ovarian and endometrial carcinomas: The case for pseudo-metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr PR07.
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