Prognostic role of p16 gene methylation in diffuse large B-cell lymphoma

Backgroundand aim Diffuse large B-cell lymphoma (DLBCL) is a high-grade, aggressive cancer. P16 gene is essential for the regulation of normal cell cycles. P16 methylation has been identified as one of the epigenetic events contributing to the pathophysiology of DLBCL with varying frequency. We aimed to investigate p16 methylation in DLBCL, its association with clinicopathological parameters, and survival analysis. Patients and methods The current retrospective cohort study includes 93 formalin-fixed paraffin-embedded tissue blocks of cases with DLBCL diagnosed histopathologically and confirmed by immunohistochemistry. Additionally, all cases were evaluated for p16 gene methylation using methylation specific-PCR technique. Results The study revealed that p16 methylation is significantly associated with increased serum lactate dehydrogenase level ( P =0.003), activated B-cell type of DLBCL ( P <0.001), bone marrow involvement ( P =0.004), poor response to therapy ( P <0.001). With respect to the analysis of survival, the advanced disease stage, along with high Eastern Cooperative Oncology Group and high-risk International Prognostic Index and bone marrow involvement, were substantially linked to poor relapsing-free survival (RFS) and overall survival (OS). Moreover, p16 methylation is significantly associated with poor OS ( P =0.008) and shorter RFS ( P =0.023). The multivariate analysis for OS indicated that P16 methylation is an independent prognostic factor in DLBCL ( P =0.002, hazard ratio=27.415, 95% confidence interval: 3.465–216.88). Conclusion It was found that p16 methylation evaluation by methylation-specific PCR is a valuable marker for therapy response prediction. Furthermore, p16 methylation is an independent prognostic parameter for RFS and OS.