Study on the relationship between protein expression and gene abnormalities of myc, bcl-2 and bcl-6in diffuse large B-cell lymphoma / 白血病·淋巴瘤

ABSTRACT

Objective To study the frequency of diffuse large B-cell lymphoma (DLBCL) with multi-genetic alteration, and its correlation with c-myc, bcl-2 and bcl-6 protein expression. Methods 50 cases diagnosed with DLBCL from January 2012 to December 2016 were collected. The expression of c-myc, bcl-2 and bcl-6 was analyzed by immunohistochemistry. Interphase fluorescence in situ hybridization (I-FISH) analysis was performed to identify the genetic alteration of c-myc, bcl-2 and bcl-6. Results In all cases, there were 27 males and 23 females with a median age of 50 years (range 3-85 years). 23 (46.00 %) cases were defined as primary nodal DLBCL and 27 (54.00 %) cases were primary extra-nodal DLBCL, with gastrointestinal tract (48.15 %, 13/27) being the most common site of involvement. c-myc protein expression was detected in 94.00 % (47/50) cases, in which 82.00 % (41/47) cases exhibited high levels of c-myc expression with positive nuclear staining observed in over 40.00 % of tumor cells. The positive rate of bcl-2 protein was 84.00 % (42/50), 76 % (38/50) cases presented with high-level bcl-2 expression. Concurrent high expression of c-myc and bcl-2 were presented in 18 cases (36.00%). FISH analysis demonstrated c-myc gene rearrangement in 7 cases (14.00 %) and amplification in 2 cases (4.00 %). bcl-2 gene rearrangement was detected in 6 cases (12.00 %) and 4 cases (8.00 %) exhibited gene amplification. bcl-6 gene rearrangement was identified in 8 cases (16.00%), amplification in 3 cases (6.00%), and 1 case concomitantly harbored the rearrangement and amplification of bcl-6. Multi-genetic alterations were defined in 4 cases with 3 cases fulfilling the criteria for double-hit lymphoma (DHL) and 1 case for triple-hit lymphoma (THL). For the cases with concomitant high-level expression of c-myc and bcl-2 proteins, 3 cases (16.67 %) was detected with multi-genetic alterations, including 2 cases for DHL and 1 case for THL. Conclusions The proportion of DLBCL with multi-genetic alterations is 8.00 % in this study. The genetic alterations are not consistently correlated with the protein expression. The molecular genetic testing is reliable for the identification of DHL.