Co-localization of EBV and Expression of P16- Cyclin-Dependent Kinase inhibitor Protein in Tissues from Patients with Non- Hodgkin's Lymphoma


background: EBV has been classified as a group 1 carcinogen associated with a variety of lymphoid and epithelial cancers. EBV was evidenced as a monogenic virus from its ability to transform normal human B cells, resulting in immortalization of the infected cells. A tumor suppressor protein, P16, is a cyclin-dependent kinase inhibitor plays a critical molecular role in cell senescence, regulation of the apoptosis pathway and G1 cell cycle arrest.Aim of the study: To analyze the concordant frequency and impact of P16 protein expression and EBV infection on tissues from a group of patients with Non- Hodgkin's Lymphoma (NHL).Patients and methods: Forty-five (45) formalin-fixed, paraffin- embedded tissues from lymph nodes biopsies were enrolled in this study; (30) lymph nodes biopsies were related to patients with NHL and (15) lymph nodes autopsies have included as apparently normal control group. Detection of EBV was done by ultra-sensitive version of in situ hybridization (ISH) method whereas immunohistochemical (IHC) system was used to demonstrate the protein expression of P16 tumor suppressor gene.Results: Detection of EBV -ISH reactions in tissues with NHL was observed in 17 out of 30 (56.7%), while in the tissues from lymph nodes autopsies was detected in 6.7% (1 out of 15).Positive P16- IHC reactions were observed in 14 out of 30 NHL cases (47.1%). No P16 positive – IHC reaction was detected in healthy lymph node tissues in the control group. The differences between the percentages of EBV and P16 detection in NHL tissues and control tissues group were statistically highly significant (P value = < 0.0001). Conclusions: The significant protein expression of P16 tumor suppressor gene as well as EBV infection in NHL in our results could indicate that cell cycle dysregulation and EBV-related transformation are important events in the pathogenesis of subset of NHL.