ABCL-523 Immunohistochemical (IHC) Expression of Epigenetic Regulators (EZH-2 and H3K27) as well as Cell Cycle Regulators (P16, P53 and RB) in Patients Diagnosed With Primary Diffuse Large B-Cell Lymphoma (DLBCL) and Association With Therapy Response Rates and Survival

Abstract

Despite advancements in chemotherapeutics, survival rate in DLBCL remains 50% in developing countries. Transcriptomic profiling has shown that EZH-2 has a role in germinal center B-Cell (GCB) type of DLBCL, NOS. To evaluate IHC expression of epigenetic regulators and cell cycle regulators in DLBCL, NOS and correlate with cell of origin (GCB type and non-GCB type), therapy response and patient survival. A retrospective study of patients diagnosed with primary DLBCL, NOS in 2014-2015 who were followed-up until April 2022. DLBCL was classified by Han's Algorithm and IHC for EZH-2, H3K27, P16, P53, RB was done & scored semi-quantitatively. Various clinical parameters at baseline as well as treatment modalities given were also noted. Study conducted at a tertiary referral cancer care center on patients visiting the out-patient department. Patients were selected continuously from the out-patient records of the Department of Medical Oncology during 2014-2015. 37 patients were included, out of which follow-up data was available for 21 patients. Association between IHC expression and various clinical parameters as well as correlation with cell of origin, therapy response and patient survival. Out of 37 patients, 62.16% were male, with male to female ratio of 1.64. Age (48.6±14.1) ranged from 22-78 years. 15/37(40.5%) patients were diagnosed as DLBCL-GCB type. 18/37(48.6%) patients presented with at least one B-symptom. 20/37(54%) patients presented at higher stage of disease (3 or 4), while 17/37(46%) had extra-nodal involvement. Derived neutrophil-lymphocyte ratio (dNLR) was ≥ 2.2 in 13/37(35%) patients. Association of H3K27 with RB(p=0.024) and EZH-2 with P53(p=0.001) was found to be statistically significant. No other significant association was found between the various markers as well as with the cell of origin. However, association of H3K27 with response rate (RR)(p=0.012) and EZH-2 with RR(p=0.028) was found to be statistically significant. EZH-2 pathway has been described in GCB type of DLBCL. Though IHC expression contributed to a statistically significant difference in RR, the expression was not limited to GCB subtype as defined by Han's Algorithm. Therefore, further larger studies are required for validation of IHC based expression. AIIMS, Delhi.