p53 and β-Catenin Expression in Gallbladder Carcinoma: Translational Insights for Pediatric Cancer Biology.

Abstract

Background: The tumor suppressor p53 and the Wnt pathway effector β-catenin represent two of the most frequently dysregulated molecular components across human malignancies. Although gallbladder cancer (GBC) predominantly affects adults, the pattern and clinicopathological correlates of p53 and β-catenin dysregulation in GBC may illuminate how these pathways behave in different biological contexts, including developmental and pediatric oncological settings, where analogous pathway alterations drive distinct tumor types.

Objective: To characterize p53 and β-catenin expression patterns in gallbladder carcinoma by immunohistochemistry, correlate findings with clinicopathological parameters, and discuss in a qualified, hypothesis-generating framework the parallels and divergences between these pathway alterations and those reported in pediatric malignancies.

Methods: A cross-sectional study analyzed 61 neoplastic and 49 non-neoplastic gallbladder lesions (2017-2021) using standardized immunohistochemistry for p53 (clone DO-7; Dako/Agilent, 1:100) and β-catenin (clone E247; Abcam, 1:200). Expression patterns were correlated with clinicopathological parameters using chi-square and Fisher's exact tests. Findings were discussed in the context of published pediatric cancer literature, with explicit acknowledgment of inter-study methodological heterogeneity.

Results: p53 overexpression (defined as >20% nuclear positivity) occurred in 78.2% of GBC cases versus 11.1% of benign lesions, correlating significantly with tumor grade and stage (p<0.05). Aberrant β-catenin expression (cytoplasmic/nuclear) was observed in 81.8% of malignant cases, with nuclear localization in 36.3%, correlating with poor differentiation. These patterns qualitatively parallel though are not directly quantitatively comparable to those reported in pediatric hepatoblastoma, Wilms' tumor, and pediatric sarcomas.

Conclusion: p53 and β-catenin dysregulation in GBC exhibits qualitative parallels to patterns reported in pediatric cancers, suggesting shared oncogenic pathway biology. These observations are hypothesis-generating and warrant validation through functional studies in appropriate preclinical models before therapeutic implications can be drawn.