Ramazan Oguz Yuceer

The prognostic and therapeutic potential of Claudin-6 and Trop-2 expression as targeted biomarkers in serous ovarian cancer: An observational study

This study aimed to evaluate the prognostic and predictive significance of Claudin-6 and trophoblast cell surface antigen-2 (Trop-2) expression in serous ovarian carcinoma, assessing their influence on treatment efficacy and clinical outcomes. A retrospective cohort of 73 patients diagnosed with serous ovarian carcinoma was analyzed. All patients underwent standard cytoreductive surgery, with or without neoadjuvant or adjuvant chemotherapy. Immunohistochemistry was used to assess the expression levels of Claudin-6 and Trop-2. Survival outcomes were evaluated using Kaplan–Meier and Cox proportional hazards models, with overall survival (OS) as the primary endpoint. High Trop-2 expression was observed in 67.1% of the patients, while 46.6% exhibited high Claudin-6 expression. Both markers were more common in older, postmenopausal patients, those with larger tumors, and those with distant metastasis. However, no significant associations were found with clinical factors (P > .05). Survival analysis demonstrated that high Trop-2 and Claudin-6 expression were associated with shorter OS and progression-free survival (PFS). Patients with high Trop-2 expression exhibited a median OS of 38 months and PFS of 32 months, whereas those with low Trop-2 expression had a median OS of 62 months and PFS of 60 months (OS: P = .039, PFS: P = .020). Similarly, high Claudin-6 expression was associated with a median OS of 32 months and PFS of 21 months, compared to an OS of 60 months and PFS of 56 months in patients with low Claudin-6 expression (OS: P = .005, PFS: P = .003). Both univariate and multivariate analyses confirmed that advanced age, and high Trop-2, and high Claudin-6 expression were significant predictors of poor OS and PFS (P < .05). These findings underscore the prognostic significance of Claudin-6 and Trop-2 in ovarian cancer, with elevated expression correlating with poorer survival outcomes. These markers may serve as independent prognostic factors, and their targeting through antibody–drug conjugates offers a potential therapeutic strategy to improve survival outcomes and overcome treatment resistance.

HER3 and FOLR1 Expression as Actionable Targets in High-Grade Serous Ovarian Carcinoma: Prognostic and Therapeutic Implications

Background and Objectives: High-grade serous ovarian carcinoma (HGSC) is characterized by aggressive tumor behavior, frequent recurrence, and limited long-term survival. Despite the established clinicopathological prognostic factors, significant heterogeneity in clinical outcomes persists, highlighting the need for biologically relevant molecular biomarkers. HER3 and folate receptor alpha (FOLR1) have promising prognostic biomarkers in ovarian cancer; however, the combined biological and prognostic impact of these two molecules has not yet been clearly demonstrated. Materials and Methods: This retrospective observational study included 66 patients with histopathologically confirmed HGSC. The immunohistochemical expression of HER3 and FOLR1 was evaluated using a standardized immunoreactivity scoring system. Associations with clinicopathological features were analyzed, and survival outcomes were analyzed using Kaplan–Meier analysis and Cox proportional hazards regression models. Results: High HER3 expression was significantly associated with distant metastasis and was identified as an independent adverse prognostic factor for both overall survival (OS) and progression-free survival (PFS). FOLR1 expression was associated with OS in univariate analysis, but did not retain independent prognostic significance in multivariate models. A moderate yet statistically significant positive correlation between HER3 and FOLR1 expression was observed, suggesting a potential association between proliferative signaling and metabolic pathways that may warrant further mechanistic investigation. Conclusions: Our findings demonstrate that HER3 is a robust prognostic biomarker in HGSC and support a biologically relevant HER3–FOLR1 interaction contributing to tumor aggressiveness. These results provide a translational rationale for combined biomarker assessment and for the development of HER3- and FOLR1-targeted therapeutic strategies, particularly antibody–drug conjugates, for HGSC.