EZH2 Upregulation Reflects Proliferation and Disease Stage in Mycosis Fungoides

Abstract:

Enhancer of Zeste Homolog 2 (EZH2) , the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2), mediates histone H3 lysine 27 trimethylation (H3K27me3) and plays an important role in epigenetic transcriptional repression and oncogenesis. Although EZH2 mutations are well characterized in B-cell lymphomas, its role in cutaneous T-cell lymphomas, including mycosis fungoides (MF), remains incompletely understood. The aim of this study was to evaluate EZH2 expression in MF using immunohistochemistry and to investigate its association with clinicopathologic parameters and proliferative activity. A total of 46 patients with MF were retrospectively analyzed. The cohort comprised 41 patients with early-stage disease (IA–IB) and 5 patients with more advanced disease manifestations (plaque and tumor lesions, including stage IIB cases). Nuclear EZH2 expression was semiquantitatively scored, and the Ki-67 proliferation index was assessed. Associations between EZH2 expression and clinicopathologic variables were analyzed using nonparametric statistical tests, including the Kruskal–Wallis and Spearman correlation tests. EZH2 expression increased progressively with advancing disease stage and lesion morphology ( P < 0.05). A significant positive correlation was observed between EZH2 expression and disease stage (r = 0.342; P = 0.02), and with the Ki-67 proliferation index (r = 0.575; P < 0.001). EZH2 expression showed no significant association with serum lactate dehydrogenase levels, β ₂ -microglobulin levels, age, sex, or disease duration. The relatively small sample size, particularly the limited number of advanced-stage cases, and the retrospective design represent study limitations. These findings demonstrate that EZH2 expression parallels disease progression and proliferative activity in MF and suggest that EZH2 immunohistochemistry may serve as a useful adjunct marker reflecting biological disease activity in routine dermatopathologic evaluation.