C-MYC and BCL2: Correlation between Protein Over-Expression and Gene Translocation and Impact on Outcome in Diffuse Large B Cell Lymphoma

Abstract

Background: Due to lack of availability of gene expression profiling (GEP) for most developing countries and<br />clinicians; the immunohistochemistry (IHC) is mostly used in the clinical application. The aim of our study is to check<br />the possibility of using IHC to detect MYC and BCL2 in our patients with diffuse large B-cell lymphoma (DLBCL)<br />instead of GEP to stratify them into high and low-risk groups. This will help in a proper treatment choice of subsequent<br />improvement in the survival outcome. Method: During the study period, 90 DLBCL patients were eligible. MYC and<br />BCL2 evaluated by IHC and gene rearrangement by real-time PCR (RT-PCR) and correlated with clinical-pathological<br />features and survival. Results: Through IHC, the expression of MYC, BCL2, and double expression was detected<br />in 35.6%, 46.7% and 30% of patients, respectively. While by RT-PCR, it was 4.53±0.74 for MYC compared with<br />2.18±0.78 for BCL-2. Most patients with BCL2+/MYC+; double-expressor and double-hit lymphomas (DEL and<br />DHL) had high stage (III, IV), more extra-nodal involvement, (P value <0.001) and intermediate to high International<br />Prognostic Index (IPI) risk profile (P-value <0.001). The median overall survival was 14 months and 6 months for DEL<br />and DHL, respectively. While all patients with DHL died during the follow-up period, the median PFS were only 2<br />months for DEL. There was a statistically significant correlation between mRNA of MYC and BCL2 with their protein<br />expression (p<0.001). Conclusion: Our results confirmed the unique characters and poor outcome associated with<br />DEL and DHL mandated the need for more intense therapy and not the standard protocol. Moreover, the significant<br />correlation between protein overexpression and gene rearrangement may open the door for the possibility to use IHC<br />instead of RT-PCR in developing countries.