The importance of Myd88 L265P mutation, clinical and immunohistochemical prognostic factors for the survival of patients with diffuse large B-cell non-Hodgkin lymphoma treated by immunochemotherapy in southeast Serbia

Abstract

Purpose: Immunochemotherapy used in the treatment of non-Hodgkin diffuse large B-cell lymphoma (DLDCL) modifies the course of disease and has a positive effect on overall survival (OS). The purpose of this study was to verify the existence of the important Myd 88 mutation and other im- munohistochemical factors on disease prognosis in patients with DLBCL in southeast Serbia. Methods: Immunohistochemical expression of CD10, Bcl- 2, Bcl-6, Ki-67 and MUM 1 was performed using paraffin blocks of DLBCL. Molecular-genetic study of MyD88 L265P gene polymorphism was done by isolation of genomic DNA from paraffin embedded tissue by means of polymerase chain reaction (PCR). Results: Immunochemotherapy (rituximab+CHOP/R-CHOP) significantly improved the overall survival (OS) of patients with DLBCL compared with patients treated with CHOP alone (p <0.0001). OS in the R-CHOP group was longest in patients with International Prognostic Index (IPI) 2 score (p=0.012) and IPI 4 score (p=0.024). Patients with Bcl-2 +, and MUM 1+ benefited from R-CHOP and their expression had no effect on OS. Analysis of restriction fragment length on the genotnic DNA showed a homozygous normal TT genotype. Conclusion• Addition of rituximab to CHOP standard protocol improved the OS rate in patients with DLBCL and altered the character and significance of previously recognized prognostic factors. IPI score in the immunochemotherapy era could not reveal possible predictive factors of poor prognosis which would help identify a high-risk subgroup of newly diagnosed DLBCL In the patient population from Southeast Serbia pathological signaling pathway achieved by Myd 88 L265 mutation was not responsible for the development of DLBCL.