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/Objectives: Claudin-18.2 (CLDN18.2) has recently emerged as a therapeutic target in gastric cancer; however, its prognostic relevance in the neoadjuvant setting remains insufficiently defined. We evaluated the clinical significance of CLDN18.2 and fibroblast growth factor receptor 2b (FGFR2b) expression in patients with locally advanced gastric cancer treated with neoadjuvant therapy. Methods: This retrospective single-center study included 64 patients with locally advanced gastric cancer who received neoadjuvant chemotherapy followed by curative surgery. Pretreatment endoscopic biopsy specimens were analyzed using immunohistochemistry to assess CLDN18.2 and FGFR2b expression. Survival outcomes were evaluated using Kaplan–Meier analysis and Cox proportional hazards regression models. Results: CLDN18.2 positivity was detected in 29.7% of patients and was not associated with baseline clinicopathological characteristics or pathological treatment response. However, CLDN18.2-positive tumors demonstrated significantly shorter relapse-free survival (median 19.0 vs. 36.6 months, p = 0.038) and overall survival (median 28.9 vs. 53.4 months, p = 0.005). In multivariable analysis, CLDN18.2 positivity remained an independent predictor of relapse-free survival. FGFR2b positivity was observed in 14.1% of patients and was evaluated descriptively due to limited case numbers. Conclusions: CLDN18.2 expression may represent a clinically relevant prognostic biomarker reflecting aggressive tumor biology in locally advanced gastric cancer treated with neoadjuvant therapy.

Pretreatment Hemoglobin, Albumin, Lymphocyte, and Platelet Score Predicts Pathological Response and Postoperative Pathological Findings in Locally Advanced Gastric Cancer - Journal of Oncological Sciences

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.

Background/Objectives: Pathological response after neoadjuvant chemotherapy is an established prognostic factor in locally advanced gastric cancer, but it does not fully reflect the biological heterogeneity of residual disease. The immune microenvironment may provide additional prognostic information. We therefore investigated the relationship between post-neoadjuvant Immunoscore, pathological findings, and disease-free survival in patients with microsatellite-stable locally advanced gastric cancer. Methods: This retrospective, single-center study included patients with locally advanced gastric adenocarcinoma who received four cycles of neoadjuvant FLOT followed by curative-intent gastrectomy between November 2023 and May 2025. Immunoscore was determined in post-neoadjuvant resection specimens based on CD3⁺ and CD8⁺ T-cell infiltration in the tumor center and invasive margin. Immunoscore assessments were performed by two pathologists blinded to clinical and outcome data, with final evaluations established through consensus review. Associations between Immunoscore and clinicopathological features were examined, including exploratory multivariable analyses adjusting for baseline clinical T stage and histological subtype. Disease-free survival was analyzed using the Kaplan–Meier method and Cox proportional hazards regression. Results: The final analysis included 48 patients. Compared with the low-Immunoscore group, the high-Immunoscore group had lower rates of ypT4 disease (37.5% vs. 75.0%; p = 0.014), ypN3 disease (21.9% vs. 68.8%; p = 0.002), and perineural invasion (43.8% vs. 75.0%; p = 0.041). The association between low Immunoscore and ypN3 disease persisted after adjustment for baseline clinical T stage and histological subtype (adjusted OR 5.89, 95% CI 1.32–26.23; p = 0.020). Tumor regression grade did not differ significantly between the groups (p = 0.211). During a median follow-up of 18.0 months, 17 patients developed recurrence. Disease-free survival was numerically longer in the high-Immunoscore group. The difference was not significant by the log-rank test (p = 0.100), whereas an exploratory Breslow analysis showed a difference between the survival distributions (p = 0.025). However, Cox regression did not demonstrate a statistically significant association with disease-free survival (HR 0.47, 95% CI 0.18–1.21; p = 0.117). Conclusions: A higher post-neoadjuvant Immunoscore was associated with less advanced residual tumor and nodal disease and less frequent perineural invasion, without a statistically significant association with tumor regression grade or disease-free survival in the primary analyses. Immunoscore may therefore complement conventional pathological assessment after neoadjuvant FLOT. These findings require validation in larger prospective cohorts.