Molecular Signature Distinguishes Between Primary Mediastinal B-Cell Lymphoma and Diffuse Large B-Cell Lymphoma with Primary Involvment of Mediastinal Lymph Nodes

Abstract

Abstract 2654 Background.Primary mediastinal (thymic) B-cell lymphoma (PMBL) has been recognized as a subtype of diffuse large B-cell lymphoma (DLBCL). It has its distinctive clinical and morphological features but differs from other types of DLBCL due to peculiar immunophenotype and gene expression profile. PMBL have a distinct gene signature with several highly expressed genes including MAL, JAK2, PDL1, PDL2 and TRAF1. PMBL molecular signature was associated with a more favorable survival compared to DLBCL cases with a non-germinal and germinal-center profile, supporting a distinct natural history for PMBL [A. Rosenwald et al., 2003, G. Lenz et al., 2008]. Aim.The aim of our study was to determine whether the quantitative expression analysis of JAK2, MAL, PDL1, PDL2 and TRAF1 genes may distinguish PMBL cases from other variants of DLBCL with primary involved of mediastinal lymph nodes. Patients and methods.31 patients with DLBCL with primary involvement of mediastinal lymph nodes and 12 patients with DLBCL without involvement of mediastinal lymph nodes were enrolled in the study. The diagnosis was made by morphological and immunophenotypic analysis of lymph nodes biopsy samples. Six healthy donors of lymphocytes constituted control group. The expression of JAK2, MAL, PDL1, PDL2 and TRAF1 genes was analyzed with RQ-PCR TaqMan hydrolyzing probes. Results.Normal median value of JAK2, MAL, PDL1, PDL2 and TRAF1 gene expression have been established according the data obtained in the set of normal donors. The gene was considered to be overexpressed if its value was more than normal median value + 3SD. In 12 patients with DLBCL without involvement of mediastinal lymph nodes there was no overexpression of MAL, PDL1 and PDL2 genes. In this group only 1 of 12 (8%) pts has the overexpression of JAK2 and 2 out of 12 (16%) pts the overexpression of TRAF1. In patients with DLBCL with primary involvement of mediastinal lymph nodes JAK2 gene was overexpressed in the 18/31 cases (58%), MAL–in the 6/31 (19%), PDL1–in the 2/31 (6%), PDL2–in the 5/31 (16%) and TRAF1–in the 2/31 (6%). Based on the overexpression of more than 3 genes we have separated from DLBCL group (31 cases) a distinct group with primary mediastinal (thymic) B-cell lymphoma 18/31 (58%) patients. So, in PMBL we revealed significant overexpression of at least 3 genes in 18/18 pts whereas in DLBCL with primary involvement of mediastinal lymph nodes no cases have such expression. Summary.Our data suggest that the quantitative molecular analysis of JAK2, MAL, PDL1, PDL2 and TRAF gene expression enables to distinguish PMBL from DLBCL with primary involvement of mediastinal lymph nodes. Disclosures:No relevant conflicts of interest to declare.