Background/Objectives: High-grade serous ovarian carcinoma (HGSC) is the most aggressive subtype of epithelial ovarian cancer and is characterized by marked heterogeneity of the tumor immune microenvironment. SET morphology has been associated with homologous recombination deficiency and BRCA1/2 mutations; however, its relationship with the immune microenvironment and progression-free survival (PFS) remains insufficiently understood. This study investigated the association between SET morphology, immune microenvironment characteristics, and PFS in patients with advanced-stage HGSC. Methods: A retrospective cohort of 305 patients with FIGO stage III–IV HGSC treated with primary surgery between 1996 and 2021 was analyzed. Histopathological assessment included evaluation of SET morphology, stromal and intraepithelial tumor-infiltrating lymphocytes (sTILs and itTILs), tumor immune phenotype, and lymphoid aggregates. Immunohistochemical analyses included CD8 and PD-L1 expression. Associations between SET morphology and immune parameters were evaluated using χ² and logistic regression analyses. PFS was assessed using Kaplan–Meier analysis, log-rank testing, and Cox proportional hazards regression. Results: SET morphology was significantly associated with higher sTIL and itTIL levels, increased stromal and intraepithelial CD8⁺ T-cell infiltration, higher PD-L1 TPS and CPS, more frequent primary and secondary lymphoid aggregates, and a predominance of the inflamed immune phenotype (all p < 0.05). Despite these features of an immune-active tumor microenvironment, SET morphology, CD8⁺ T-cell density, PD-L1 expression, lymphoid aggregates, and immune phenotype were not independently associated with prolonged PFS. In contrast, age remained an independent prognostic factor, with patients older than 55 years having a 50% higher risk of disease progression than younger patients (HR = 1.5, 95% CI: 1.1–2.1; p = 0.012). Higher intraepithelial TIL levels (>10%) were independently associated with improved PFS (HR = 2.1, 95% CI: 1.0–4.4; p = 0.045). Conclusions: SET morphology identifies an immune-active subtype of HGSC characterized by increased immune infiltration and PD-L1 expression but does not independently predict prolonged PFS. The dissociation between immune cell abundance and clinical outcome suggests that immune cell functionality, rather than immune infiltration alone, may determine prognosis. Routine histopathological assessment of SET morphology may facilitate biological characterization of HGSC and provide a practical surrogate marker for future biomarker-driven studies evaluating immunotherapy and targeted treatment strategies.

Background: Appendiceal epithelial lesions are rare and heterogeneous. Evidence regarding vascular endothelial growth factor A (VEGF-A) expression in localized appendiceal lesions is limited. We compared VEGF-A immunoreactivity across diagnostic subtypes and explored associations with histological features. Methods: This retrospective exploratory study included 73 appendiceal neoplastic epithelial lesions. Formalin-fixed, paraffin-embedded tissue was assessed for predominant VEGF-A staining intensity and percentage of positive neoplastic epithelial cells. Their product was reported as a modified immunoreactivity score (0–300). Permutation-based nonparametric tests, Benjamini–Hochberg correction, diagnosis-adjusted sensitivity analyses, and interobserver agreement analyses were used. Results: VEGF-A staining was present in 71/73 cases. Median immunoreactivity scores were 205 for adenocarcinoma, 170 for hyperplastic polyp, 180 for low-grade appendiceal mucinous neoplasm, and 100 for sessile serrated lesion; the overall difference was not significant (p = 0.073). No histological-feature association remained significant after false-discovery-rate correction. Surface nuclear stratification was not significant in the global analysis (p = 0.051; q = 0.169), and after diagnosis adjustment (p = 0.282). VEGF-A measures did not differ between acute and incidental presentations; patients with acute presentations were younger (p = 0.006). Conclusions: VEGF-A immunoreactivity was common, but no robust subtype-specific or histology-specific pattern was identified. These exploratory findings do not establish clinical utility and require confirmation in larger controlled cohorts.

Background: Appendiceal epithelial lesions are rare and heterogeneous. Evidence regarding vascular endothelial growth factor A (VEGF-A) expression in localized appendiceal lesions is limited. We compared VEGF-A immunoreactivity across diagnostic subtypes and explored associations with histological features. Methods: This retrospective exploratory study included 73 histologically confirmed appendiceal lesions. Formalin-fixed, paraffin-embedded tissue was assessed for predominant VEGF-A staining intensity and percentage of positive neoplastic epithelial cells. Their product was reported as a modified immunoreactivity score (0-300). Permutation-based nonparametric tests, multiplicity correction, and diagnosis-adjusted sensitivity analyses were used. Results: VEGF-A staining was present in 71/73 cases. Median immunoreactivity scores were 205 for adenocarcinoma, 170 for hyperplastic polyp, 180 for low-grade appendiceal mucinous neoplasm, and 100 for sessile serrated lesion; the overall difference was not significant (p = 0.075). No histological-feature association remained significant after false-discovery-rate correction. Surface nuclear stratification was not significant in the global analysis (p = 0.051; q = 0.169), pairwise analysis, within-subtype analyses, or diagnosis-adjusted sensitivity analysis (p = 0.278). VEGF-A measures did not differ between acute and incidental presentations; patients with acute presentations were younger (p = 0.007). Conclusions: VEGF-A immunoreactivity was common, but no robust subtype-specific or histology-specific pattern was identified. These exploratory findings do not establish clinical utility and require confirmation in larger controlled cohorts.