Prognostic impact of c-myc gene rearrangement, presence of EBV and ki-67 index in patients with primary diffuse large Bcell lymphoma of lymph node treated with R-CHOP regimen

Diffuse large cell lymphoma B (DLBCL) is the most common (40-30%) and the most heterogeneous type of Non Hodgkin lymphoma which has aggressive clinical forms. Hans algorithm divides DLBCL into two molecular groups as Germinal Center B-cell (GCB) & Activated B-Cell (ABC) types according to immunohistochemical expression of BCL6, CD10 & MUM1. Ki-67 is a nuclear nonhistone chromatin protein that can be used as a marker of proliferation in cancer, such as lymphoma. MYC is a pleiotropic transcription factor involved in many different cellular processes. MYC translocation is a recurrent genetic alteration in aggressive B-cell lymphomas such as Burkitt’s lymphoma (BL) and DLBCL. The role of EBV in DLBCL has become a discussed issue in recent years. The current standard therapy for patients with DLBCL is rituximab plus cyclophosphamide,doxorubicin, vincristine, and prednisone (R-CHOP) In this study we studied 53 eligible patients with diagnosis of primary DLBCL of lymph node, treated with R-CHOP therapy, with at least 18 months of follow up after initial diagnosis. Tissue microarray blocks was prepared. Immunohistochemical expression of Ki-67, BCL6, CD10, MUM1 and other basic diagnostic markers in addition to CISH study for EBER-1&2 expression and c-myc amplification were done. Patients aged between 18 and 86 years with an average age of 50.47 years. 31 patients (58.5%) were men and 22 (41.5%) were female. According to Hans algorithm 17(32.1%) and 36(67.9%) cases were of GCB and ABC type respectively. 20 patient(37.7%) revealed c-myc amplification, all of which were within low level. 7(13.2%)and 4(7.5%) cases showed respectively certain(> 20%) and weak(1-5%) positivity for EBER. Age average was higher in the group with no primary response to treatment (59.10 versus 48.79)(p=0.078). EBER certain positive patients had better primary response (p=0.08). c-myc amplification related with shorter progression free survival(13.85 versus 20.91) (p=0.067) and more need to adjuvant radiotherapy (p=0.03) Although there was some trends for ABC molecular type to have poorer prognosis but no significant correlation was detected. Ki-67 index also revealed no significant correlation with prognostic indexes. Older age and EBER positivity correlated with lower primary response and cases with c-myc amplification shoed shorter PFS and much need to Adjuvant radiotherapy.

Keywords:

DLBCL , EBV , c-myc , Ki-67 , R-CHOP