Background/Objectives: Epithelial ovarian cancer (EOC) is a leading cause of death among forms of gynecologic cancer. Significant causes of mortality include high recurrence rates and the development of resistance to platinum-based chemotherapy. This highlights the need for reliable prognostic biomarkers to improve patient stratification and inform treatment decisions. Claudin-4, a tight junction protein frequently overexpressed in epithelial tumors, has been associated with tumor progression and resistance to chemotherapy. Methods: We retrospectively analyzed 83 patients with EOC who underwent debulking surgery. Claudin-4 expression was assessed by immunohistochemistry and categorized as high or low based on a semi-quantitative scoring system. Survival outcomes were evaluated using Kaplan–Meier analysis and Cox regression. Predictors of platinum resistance were examined using logistic regression. Results: High Claudin-4 expression was observed in 55.4% of cases and was associated with significantly shorter disease-free survival (DFS) (23 vs. 66 months, p = 0.00024) and overall survival (OS) (85 months vs. NR, p = 0.0031). In multivariable analysis, platinum resistance (DFS; HR 4.99, OS; HR 4.27) and high Claudin-4 expression (DFS; HR 2.46, OS; HR 3.59) were independent predictors of poor outcomes. Logistic regression further demonstrated that high Claudin-4 expression and interval debulking surgery were independent predictors of platinum resistance. Conclusions: High Claudin-4 expression was associated with inferior survival and an increased risk of platinum resistance in EOC. Our findings suggest that Claudin-4 may serve as a negative prognostic biomarker and a potential therapeutic target. Future prospective studies are warranted to further elucidate the underlying mechanisms and validate Claudin-4’s clinical utility.

Background: Platinum resistance remains a major therapeutic challenge in epithelial ovarian cancer (EOC). The tumour–stroma ratio (TSR) has emerged as a potential histopathological marker of tumour biology, but its clinical significance in different clinical settings remains unclear. We evaluated the association between stromal proportion, assessed using the TSR methodology, platinum resistance, and survival outcomes in patients undergoing primary debulking surgery (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (NACT+IDS). Methods: This retrospective study included 83 patients with epithelial ovarian cancer (EOC) who underwent either primary debulking surgery (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (NACT+IDS) between 2017 and 2024. Patients were analysed separately according to treatment strategy. Stromal proportion was assessed on primary surgical specimens in the PDS cohort and on pretreatment diagnostic biopsy specimens in the NACT+IDS cohort. For this retrospective analysis, platinum resistance was operationally defined as recurrence within six months after completion of first-line platinum-based chemotherapy. Survival outcomes were analysed using the Kaplan–Meier method, and univariable binary logistic regression was performed separately within the PDS and NACT+IDS cohorts to explore the association between stromal category and platinum resistance. Results: Platinum resistance occurred in 25.3% of patients. In the PDS cohort, stromal category was not associated with clinicopathological characteristics, platinum resistance, disease-free survival (DFS), or overall survival (OS). In the NACT+IDS cohort, patients in the stroma-high group had a numerically higher rate of platinum resistance than those in the stroma-low group (57.9% vs. 22.2%; Fisher’s exact p = 0.114). Based on univariable logistic regression analysis, the stroma-high group had higher estimated odds of platinum resistance (OR 4.81, 95% CI 0.78–29.40), although this finding did not reach statistical significance (p = 0.090). No significant association was observed between stromal category and survival outcomes in either cohort. Conclusions: In the NACT+IDS cohort, patients in the stroma-high group had a numerically higher rate of platinum resistance than those in the stroma-low group; however, this difference did not reach statistical significance. These results should be interpreted with caution due to the retrospective study design and limited sample size; however, they nonetheless support further investigation of pretreatment TSR as a simple and easily applicable histopathological parameter in EOC. Larger prospective multicentre studies are required to determine whether this exploratory signal is reproducible and clinically relevant.