Human epidermal growth factor receptor-2, nectin-4, and trophoblast cell surface antigen-2 expression varies significantly across ovarian cancer histotypes

OBJECTIVE: Patients with advanced-stage ovarian cancer (OC) have limited therapeutic options. Antibody-drug conjugates (ADCs) targeting human epidermal growth factor 2 (HER2), nectin-4, and trophoblast cell surface antigen 2 (TROP2) have shown efficacies in various cancers and may benefit patients with OC. The antigen expression may vary across histotypes and affect patient selection but relevant data is variable in OC. This study aimed to evaluate the expression of HER2, nectin-4, and TROP2 in an OC cohort comprising different histotypes with clinicopathological correlation. MATERIALS AND METHODS: Patients diagnosed with high-grade serous carcinoma (HGSC), clear cell carcinoma (CCC), endometrioid carcinoma (EC), or mucinous carcinoma (MC) of the ovary between 2021 and 2023 were retrospectively collected. Demographics and pathological slides were reviewed. HER2, nectin-4, and TROP2 immunohistochemical stains were performed and scored (HER2, ASCO/CAP gastroesophageal adenocarcinoma guidelines; nectin-4 and TROP2: H-score). RESULTS: Ninety-two cases were collected, including 33 HGSC, 27 EC, 24 CCC, and eight MC. Three (3.3%) cases showed HER2 positivity (score 3+), significantly more common in MC (25.0%) than in HGSC (0%, P = 0.034) and EC (0%, P = 0.047). Forty-two (45.7%) cases showed weak nectin-4 expression (median H-score: 10), significantly lower in CCC (median H-score: 0) than in HGSC (median H-score: 15, P < 0.001), EC (median H-score: 17, P = 0.001), and MC (median H-score: 17, P = 0.002). Fifty-nine (64.1%) cases showed weak to strong TROP2 expression (median H-score: 30), significantly higher in EC (median H-score: 62) than in HGSC (median H-score: 29, P = 0.026), CCC (median H-score: 8, P < 0.001), and MC (median H-score: 35, P = 0.027), and significantly higher in HGSC than in CCC (P = 0.022). CONCLUSIONS: HER2, nectin-4, and TROP2 expression showed significant variation across ovarian cancer histotypes.