Human epidermal growth factor receptor-2, nectin-4, and trophoblast cell surface antigen-2 expression in endometrial carcinosarcoma

Objective

To characterize the immunohistochemical expression of human epidermal growth factor receptor-2 (HER2), nectin-4, and trophoblast cell surface antigen-2 (TROP2) in endometrial carcinosarcoma (ECS), with particular attention to compartment-specific expression patterns and potential therapeutic implications.

Methods

We retrospectively analyzed 56 ECS cases and performed immunohistochemistry for HER2, nectin-4, and TROP2 on representative tumor sections. Expression levels were semi-quantitatively scored and compared between the carcinomatous and sarcomatous components. Associations with clinicopathological features were also assessed.

Results

HER2 overexpression (3+) was identified in 4 cases (7.1 %), with an additional 6 cases (10.7 %) showing equivocal (2+) staining. HER2 2+/3+ expression was significantly associated with serous carcinoma differentiation (31.0 % vs. 3.7 %, P = 0.012) and was largely confined to the carcinomatous component (P < 0.001). Nectin-4 was expressed in 39.3 % of cases, predominantly weak in intensity, with significantly higher expression in the carcinomatous than in the sarcomatous component (P < 0.001). TROP2 expression was observed in 62.5 % of cases, also confined to the carcinomatous component, with no strong expression detected. No significant correlations were found between marker expression and other clinicopathological variables beyond serous differentiation.

Conclusions

HER2, nectin-4, and TROP2 are preferentially expressed in the carcinomatous component of ECS. HER2-targeted antibody–drug conjugates may be a promising therapeutic strategy for ECS with serous carcinoma differentiation. Further investigation is warranted to determine the clinical relevance of targeting nectin-4 and TROP2 in ECS.