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

Document Type: Research Articles

Authors

1 Department of Medical Oncology, Faculty of Medicine, Zagazig University, Egypt.

2 Department of Pathology, Faculty of Medicine, Zagazig University, Egypt.

3 Department of Clinical Oncology, Faculty of Medicine, Zagazig University, Egypt.

4 Department of Biochemistry, Faculty of Medicine, Zagazig University, Egypt.

5 Department of General Surgery, Faculty of Medicine, Zagazig University, Egypt.

6 Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Suez Canal University, Egypt.

Abstract

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

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