BCL2 and subtype as prognostic and predictive markers of diffuse large B-cell lymphoma

Introduction: Since patients with similar International Prognostic Index scores have varied outcomes, molecular signatures, including BCL2 overexpression have been studied to prognosticate diffuse large B-cell lymphoma (DLBCL), which have shown varied outcomes. Objective: The aim of this study is to correlate BCL2 protein expression with survival in two biologic subgroups of DLBCL. Materials and Methods: A total of 112 adults with DLBCL between 2008 and 2012 were identified. BCL2 overexpression was determined using immunohistochemistry. Results: Median survival was greater in BCL2 negative (n = 52) than positive (n = 44) (36 vs. 24.5 months; P = 0.003). In nongerminal center B-cell type (NGCB), BCL2 negativity had a survival advantage over BCL2 positive (36.5 vs. 17 months; P = 0.02), similarly in GCB (36 vs. 33 months; P = 0.032). Of 109, 66 received CHOP and 43 R-CHOP. R-CHOP arm had a significant survival advantage over CHOP arm (38 vs. 24 months; P< 0.05). In CHOP group, GCB had a survival advantage over NGCB (32 vs. 14 months; P< 0.05). In R-CHOP group, no significant difference was seen. BCL2 negativity had a survival advantage in CHOP (31 vs. 20.5 months; P< 0.05) as well as R-CHOP group (39 vs. 26.5 months; P< 0.05). Analysis was performed in each treatment arm (CHOP and RCHOP) based on BCL2 expression (positive or negative) in GCB and NGCB arms. No statistically significant difference was seen in the four arms. Conclusions: BCL2 although an indicator of poor outcome, its use to predict outcomes alone in the absence of study of the expression of concomitant markers, such as myc/BCL6 would cause a bias in results. Furthermore, its relevance in the rituximab era needs further validation.