Epithelial-Mesenchymal Transition-Like Immunophenotypic Changes in Gallbladder Carcinogenesis: A Quantitative Digital Pathology Study
DOI:
https://doi.org/10.52340/GBMN.2026.01.01.166Keywords:
Gallbladder carcinoma, biliary intraepithelial neoplasia (BilIN 1–3), digital pathology, epithelial–mesenchymal transition, immunohistochemistry, tumor progressionAbstract
Background: Gallbladder carcinoma develops through a multistep sequence from chronic inflammation to dysplasia and invasive carcinoma. The role of epithelial– mesenchymal transition (EMT)-associated phenotypic alterations in this process remains incompletely defined. Objectives: To quantitatively evaluate immunohistochemical markers associated with EMT across the spectrum of gallbladder lesions and assess their relationship with disease progression. Methods: A retrospective multicenter study was conducted on 90 formalin-fixed paraffin-embedded gallbladder specimens collected between 2015 and 2025, including chronic cholecystitis, intestinal metaplasia, biliary intraepithelial neoplasia (BilIN 1–3), and invasive adenocarcinoma. Immunohistochemical analysis was performed for E-cadherin, β-catenin, Vimentin, CK17, CK19, and Ki67. A quantitative assessment was conducted using digital whole-slide imaging (QuPath and ImageJ). An exploratory EMT-like index was calculated based on epithelial and mesenchymal marker expression. Statistical analysis was performed using nonparametric tests and correlation analysis. Results: A progressive decrease in E-cadherin expression and a corresponding increase in Vimentin and nuclear β-catenin expression were observed across lesion categories (p<0.05). CK17 expression and the Ki-67 proliferative index were significantly elevated in dysplastic and malignant lesions compared with benign conditions (p<0.01). The EMT-like index showed a stepwise increase from inflammatory lesions to invasive carcinoma (p<0.01), indicating a shift toward a mesenchymal-associated immunophenotype during disease progression. Conclusions: Gallbladder carcinogenesis is associated with progressive immunophenotypic changes characterized by reduced epithelial marker expression, increased mesenchymal marker expression, and enhanced proliferative activity. These findings are consistent with EMT-like phenotypic remodeling during tumor progression; however, mechanistic confirmation requires further molecular investigation.References
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