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Original Article
- Clinicopathological associations and prognostic significance of EZH2, H3K27me3, pRB, p53, and p16 expression in diffuse large B-cell lymphoma
- Ishan Gupta, Surabhi Jain, Moien Rasheed Lone, Ajay Gogia, Chandan Krushna Das, Mehar Chand Sharma, Ashish Datt Upadhyay, Saumyaranjan Mallick
- J Pathol Transl Med. 2026;60(6):635-645. Published online November 13, 2026
- DOI: https://doi.org/10.4132/jptm.2026.09.14
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Abstract
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Supplementary Material - Background
Diffuse large B-cell lymphoma (DLBCL) is characterized by pronounced heterogeneity in its morphological and biological attributes, with emerging evidence highlighting the pivotal role of epigenomic alterations in its pathogenesis. This study aimed to investigate the relationship between EZH2 expression and cell-cycle regulatory proteins, focusing on their prognostic implications. Methods: This retrospective study included 131 patients with nodal primary DLBCL, who were categorized according to the Hans algorithm and additional immunohistochemistry was performed for selected epigenetic (EZH2 and H3K27me3) and cell-cycle regulatory markers (phosphorylated retinoblastoma [pRB], p16 and p53). Receiver operating characteristic (ROC) curve analysis and Cox regression models were applied to assess prognostic utility. Appropriate statistical analysis was performed. Results: EZH2 was expressed in 59.5% of cases and significantly associated with p53 (p = .003), germinal center B-cell-like (GCB) subtype (p = .031), and CD10 positivity (p = .030). pRB positivity was more frequent in the activated B-cell-like subtype (82.5% vs. 64.3%, p = .024) and was associated with MUM1 (p = .028), while p16 expression was linked to BCL6 (p = .004). ROC analyses demonstrated poor discriminatory ability for overall survival (area under the curve, 0.39 to 0.54), with no clinically actionable cutoffs identified. Stepwise Cox regression identified age >60 years (hazard ratio [HR], 2.04; p = .042) and Eastern Cooperative Oncology Group ≥ 2 (HR, 3.46; p = .001) as independent predictors of overall survival. For progression-free survival, no biomarker reached statistical significance. Conclusions: EZH2 and related cell-cycle proteins demonstrate biological associations in DLBCL but lack robust prognostic utility when assessed by immunohistochemistry. Clinical variables showed stronger predictive value for survival, while no biomarker reached statistical significance for survival, underscoring the need for integrated molecular approaches to improve risk stratification and therapeutic targeting in DLBCL.
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