EZH2 expression in colorectal carcinoma: an evaluation of clinicopathological and prognostic value

Background: Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of Polycomb Repressive Complex 2, catalyzes trimethylation of histone H3 lysine 27 and has been implicated in tumor progression. Aim: Our study aims to assess the relationship between EZH2 expression and clinicopathologic data, and survival in colorectal carcinomas (CRC). Materials and methods: EZH2 immunohistochemistry was performed on tumor blocks from 124 CRC patients. Based on H-scores, cases were stratified into low- and high-expression groups. EZH2 status was correlated with demographic, clinical, and pathologic features, and overall survival was analyzed with the Kaplan–Meier method and log-rank test. Results: A total of 124 cases of CRC; 12 (9.7%) cases were classified as low EZH2 expression, and 112 (90.3%) cases were classified as high EZH2 expression. A significant association was found between EZH2 expression and microsatellite stability. High EZH2 expression was significantly enriched in microsatellite-stable tumors (p = 0.007) and in left-sided lesions (p = 0.049). No significant associations were detected with sex, stage, grade, lymph-node status, or vascular invasion. Kaplan–Meier analysis revealed no difference in overall survival between low- and high-EZH2 groups (log-rank p = 0.47; hazard ratio = 1.13, 95% CI 0.45–2.85). EZH2 staining was uniformly strong in normal mucosa and adenomas, mirroring the high expression observed in most CRCs. Conclusions: EZH2 is highly expressed across the normal-adenoma-carcinoma sequence and, in our cohort, was not linked to overall survival or to most clinicopathologic parameters in CRC. The lower expression observed in a subset of MSI-H tumors warrants further investigation; present evidence remains insufficient to establish EZH2 as an independent prognostic biomarker. © The Author(s) 2025.