VEGF-A Immunohistochemical Expression Across Appendiceal Epithelial Lesions: A Retrospective Exploratory Study

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.