Molecular Characterization of Diffuse Large B Cell Lymphoma and Its Prognostic Significance

Abstract

Lymphomas are a diverse group of malignant neoplasms that arise from clonal expansion of neoplastic B and T lymphocytes derived from normal counterparts in the immune system. Lymphomas are broadly classified into Hodgkin s lymphoma and non Hodgkin s Lymphoma. The current World Health Organization (WHO) classification of lymphomas provides an up-to-date and biologically relevant approach to lymphomas by incorporating a variety of parameters (morphology, immunophenotypic findings, molecular genetic studies and cytogenetic features) and has become the gold standard. OBJECTIVES: 1. To classify DLBCL into Germinal Center B like (GCB) and Activated B like (ABC) subtypes using Bcl-6, CD10, Mum1 antibodies and determine the clinical significance and prognostic value of the differentiation profile. 2. To evaluate the protein expression patterns of cell cycle regulatory proteins (p16, p14, p21, p27, CyclinD2, CyclinE, CyclinA, CyclinB1), tumour suppressor proteins (p53, Blimp 1), oncoprotein mdm2, proliferative marker (Ki 67), apoptosis-regulating proteins (Bcl-2, Bax) and NF-kB in patients with DLBCL and assess the relationship of these proteins to overall survival. The molecular characterization of DLBCL and the study of various cell cycle regulatory and apoptotic proteins showed statistically significant influence on prognosis only in IPI status based stratification, immunophenotypic classification (GCB/ABC), p21 expression based classification and NFkB expression based classification. The other cell cycle regulatory proteins were associated with trends consistent with conventional published studies but failed to demonstrate any statistically significant conclusions. An increase in sample size may yield statistically significant results. This could also be due to the confounding effects of various other cell cycle regulatory proteins as DLBCL is a complex multihit disease with alteration of multiple survival pathways resulting in multiple drivers of tumour cells proliferation and survival.