Impact of Double Expression of C-MYC/BCL2 Protein and Cell of Origin Subtypes on the Outcome among Patients with Diffuse Large B-Cell Lymphoma: a Single Asian Center Experience

Background: Diffuse large B-cell lymphoma (DLBCL) with double expression of c-MYC and BCL2 protein is
associated with dismal outcome after treatment with R-CHOP. Local data on disease burden and survival outcome in
DLBCL is limited. We investigated the prognostic values of c-MYC/BCL2 protein co-expression and cell of origin
subtypes using immunohistochemistry (IHC) and to determine their associations with multiethnic groups under
resource limited setting. Methods: This was a retrospective study which recruited 104 patients in between June 2012
and December 2015 for IHC review and analysis. Result: We demonstrated that patients with high International
Prognostic Index (IPI) (score 3-5) and co-expression of c-MYC/BCL2 protein had significant inferior overall survival
(OS) and event free survival (EFS) respectively (P<0.05). c-MYC/BCL2 protein co-expression was more common in
non-germinal center B-cell (non-GCB) (P=0.048) and contributed to adverse prognosis in this group of patients (OS,
P=0.004; EFS, P=0.005). In multivariate analysis, double-protein co-expression was a significant independent predictor
of inferior outcome after adjusted for IPI and cell of origin subtypes (OS hazard ratio [HR], 2.11; 95% CI, 1.01 to 4.04;
P=0.048; EFS HR, 2.31; 95% CI, 1.05 to 5.04; P=0.036). In addition, non-GCB subtype was more common than GCB
in Malays (60% vs 40%, P=0.106) and Chinese (81.2% vs 18.8%, P=0.042). Indians had more DLBCL without c-MYC/
BCL2 protein co-expression compared to double-protein positive cases (66.7% vs 33.3%, P=0.414). Otherwise, the
prognostic impact of ethnicity on survival outcome was insignificant (P=0.961). Conclusion: c-MYC/BCL2 protein
co-expression in non-GCB subtype constituted a unique group with extremely inferior outcome regardless of ethnicity.
Gene expression profile (GEP) may possibly provide insights into the cause of discrepancies in DLBCL subtypes and
protein expression among the multiethnic groups.