Correlation of c-MYC, BCL2 and BCL6 proteins overexpression with prognosis in Syrian DLBCL Patients

Background and Aim: c-MYC is a potent transcription factor involved in several cellular processes, and is overexpressed in many cancers, including non-Hodgkin lymphoma (NHL). The most common subtype of NHL is diffuse large B-cell lymphoma (DLBCL). DLBCL tumors expressing both the c-MYC and BCL2 proteins, i.e. double expressor (DE), also triple expressors (TE) expressing BCL6 in addition to c-MYC and BCL2, are all more aggressive and refractory to treatment. Our study aims to investigate auxiliary immunohistochemical tests (IHC) not routinely used, namely c-MYC, BCL2 and BCL6, seeking a better prognostic testing protocol for DLBCL patients. Materials and Methods: Forty-one formalin-fixed paraffin-embedded (FFPE) DLBCL samples were collected retrospectively from the pathology laboratory at Al-Assad University Hospital after approval from the ethics committee at Damascus University. Clinical data was obtained from patients records in regards to progression-free survival (PFS) and other parameters. Slides were microtomed from each FFPE sample and used to perform IHC tests of the c-MYC, BCL2 and BCL6 oncoproteins. Fisher’s exact test was used to study the independence of protein IHC results in relation to one another and compared with PFS. Results: Statistical analysis of the c-MYC overexpression and double expressor status showed no correlation (P>0.05) with PFS in DLBCL patients. Whereas, when BCL6 IHC results were analyzed, BCL6 positivity and triple expressor status showed a significant association (P<0.05) with unfavorable PFS outcomes, where BCL6 positive patients were three times more likely to progress to an unfavorable outcome in comparison to BCL6 negative patients within three years of diagnosis Conclusions: For the determination of DLBCL prognosis, routine IHC testing for BCL6 protein overexpression is recommended. Thus, we suggest that BCL6 IHC testing should be added to the workup protocol of DLBCL patients in Syria.