Prognostic Significance of Concurrent MYC, BCL2 and/or BCL6 Expression in Diffuse Large B-Cell Lymphoma

Abstract
Background: DLCL with aberrations in MYC, BCL2 and/or BCL6 due to genetic alterations or protein expression is a high grade B-cell lymphomas with poor prognosis if received standard RCHOP chemotherapy. So that, different regimens are needed for better prognosis.
Aim of the Study: Identify the association of protein, genetic expression of MYC, BCL2, and/or BCL-6 in cases of DLBCL, if MYC IHC could be used as a screening test to determine DHL or THL status, and to determine if the DHL or THL biology are related to any clinic-pathological features.
Material and Methods: Thirty patients who were diagnosed with primary DLBCL from July 2015 to July 2018. The cases were collected from General surgery department-Faculty of medicine- Benha University and Assiut faculty of medicine-Al-Azhar University were identified after applying exclusion and inclusion criteria. Clinico-pathological data was obtained by review of medical records and biopsy specimens for IHC and FISH were obtained from the Departments of general surgery. The FISH test (for MYC, BCL2, and BCL-6) and IHC (for CD10, KI 67, MYC, BCL2, and BCL-6) were per-formed. Statistical analysis was performed using IBM SPSS Statistics for Windows, version 16 (p-valueResults: Double hit gene rearrangements by FISH were detected in 3/30 (10%) patients. MYC IHC was positive in 6/30 (20%) cases, and 3 of these 6 cases (50%) were FISH positive. Sensitivity, specificity and concordance of MYC IHC as a screening tool were 100%, 73.6% and 50%, respec-tively. BCL2 staining was positive in 14/30 (46.6%) cases, and only 3 of the 14 cases (21.4%) were FISH positive. 6/30 (20%) cases were positive for both MYC and BCL2 by IHC (double protein expresser status) and 3 of these 6 (50%) cases were positive by FISH. DHL biology showed an association with many clinico-pathological parameters including elevated serum Lactate dehydrogenase, stage III,IV, Bone marrow infiltration, extranodal involvement, and overall survival.
Conclusion: The association between MYC IHC and FISH in the current study was statistically significant. The sensitivity of MYC in our study was 100%, we can propose that it can be used as an effective screening test if similar results can be validated in larger studies. The current study supports the practice of routinely testing for MYC and BCL2 status in all cases of DLBCL, irrespective of clinical features of the disease, to identify the high-risk DHL subset of patients, who can be candidates for more intense newer chemotherapy regimens and for prognostic purposes.