p16 positivity as a potent indicator of high-grade histology and its interplay with HER2/neu in urothelial bladder carcinoma.

The significant molecular heterogeneity of urothelial bladder carcinoma (UBC) challenges its clinical management. This clinicopathological study analyzed HER2/neu and p16 expression in 40 patients with UBC (20 low-grade, 20 high-grade) using standardized immunohistochemistry. HER2/neu expression was scored per ASCO/CAP guidelines (0-3 +), and p16 status was determined via nuclear/cytoplasmic staining. p16-positive tumors demonstrated a six-fold increased likelihood of high-grade histology (OR=6.00, 95 % CI: 1.46-24.69, p = 0.010), establishing it as a robust independent marker. HER2/neu overexpression (3 +) was identified in 37.5 % of cases and correlated significantly with p16 expression (p = 0.025), suggesting pathway interplay. These results position p16 as a valuable adjunct for identifying high-grade UBC and define the HER2/neu-p16 co-expressing phenotype as a distinct molecular subset with potential therapeutic relevance. Combined assessment could refine diagnostic accuracy and risk stratification.