Genomic, Trop-2, and Immune Profiles of Carcinomatous and Sarcomatous Components in Ovarian Carcinosarcoma

Ovarian carcinosarcoma (OCS) is a rare, aggressive tumor composed of both carcinomatous and sarcomatous components, typically associated with poor prognosis. Due to its rarity, the molecular characteristics, immune microenvironment, and optimal treatment of OCS remain unclear. This study aimed to characterize the genomic profiles, Trop-2 expression, and immune microenvironment of the carcinomatous and sarcomatous components of OCS separately, and to explore candidate therapeutic targets for this rare and aggressive tumor.

This retrospective, single-institution study analyzed nine cases of ovarian or fallopian tube carcinosarcoma treated between 2013 and 2023. Targeted next-generation sequencing of 160 cancer-related genes was performed in eight cases, and immunohistochemistry for p53, Trop-2, CD8, and PD-L1 was performed in nine cases, with the carcinomatous and sarcomatous components evaluated separately whenever they were separable. All tumors contained high-grade serous carcinoma components. Targeted sequencing revealed TP53 mutations in all samples. Most genetic alterations were shared by both components, supporting the role of epithelial-mesenchymal transition in OCS pathogenesis. Amplifications in CCND1, CCNE1, PRKCI, and GNAS (37.5%), and ERBB2 (12.5%) were detected, and whole genome duplication was observed in two cases (25%). One case (12.5%) showed high microsatellite instability and was associated with Lynch syndrome. Immunohistochemistry showed Trop-2 positivity in all carcinomatous components, with a trend toward higher expression compared with sarcomatous areas (p = 0.0625). CD8 and PD-L1 levels were low, consistent with a relatively non-inflamed, immune-cold-like microenvironment.

These findings suggest molecular similarities between OCS and high-grade serous carcinoma and highlight the role of epithelial-mesenchymal transition. The low immune marker expression suggests limited benefit from immune checkpoint inhibitors, except in select Lynch syndrome cases. In contrast, the consistently high Trop-2 expression in the carcinomatous component may warrant further investigation of Trop-2-targeted antibody-drug conjugates as a hypothesis-generating therapeutic candidate for OCS.