OBJECTIVE: To comprehensively characterize the expression, clinicopathological landscape, and potential prognostic relevance of actionable antibody-drug conjugate (ADC) targets (FRα, TROP2, HER2) in high-grade serous ovarian cancer (HGSOC), evaluated across molecular strata defined by homologous recombination deficiency (HRD) status. METHODS: We retrospectively analyzed 193 patients with primary HGSOC. FRα, TROP2, and HER2 expression were assessed by immunohistochemistry. HRD status was defined by the presence of pathogenic BRCA1/2 mutations and/or a Genomic Scar Score (GSS) ≥45. Clinicopathological correlations and survival outcomes were evaluated using Kaplan-Meier analysis, univariable Cox regression, and multivariable Cox regression models with adjustment for HRD status, PARP inhibitor exposure, and anti-angiogenic therapy. RESULTS: FRα and TROP2 were frequently expressed, with high expression observed in 51.8% and 24.9% of cases, respectively, whereas 25.4% exhibited ultra-low HER2 expression. HRD-positive tumors comprised 66.3% of the cohort. High TROP2 expression was significantly associated with advanced FIGO stage (P = 0.027), whereas HER2 expression was overrepresented in BRCA-mutated tumors (P = 0.020). Triple co-expression was rare, identified in only 7.8% of cases. Multivariable Cox regression analysis demonstrated that HRD positivity was an independent favorable prognostic factor, whereas high TROP2 expression was an independent adverse prognostic factor. CONCLUSION: ADC targets display distinct expression profiles across HGSOC subgroups. The present study confirms that both HRD status and TROP2 expression are independent prognostic factors for progression-free survival. Although FRα and HER2 do not demonstrate independent prognostic significance, they remain promising candidates for targeted therapy. The integration of HRD status with ADC target expression profiling may improve patient stratification and facilitate biomarker-driven therapeutic decision-making.
Zhao et al. (Tue,) studied this question.