Prognostic Significance of Bcl-2 and Bcl-6 Immunostaining in B-Cell Non-Hodgkin's Lymphoma

Purpose: The aim of this study was to identify a possible effect of Bcl-2 and Bcl-6 proteins on the clinical behavior and outcome in different subtypes of B-cell non-Hodgkin lymphoma (B-NHL).  Methods: We retrospectively studied Bcl-2 and Bcl-6 expression by immunohistochemistry (IHC) in 145 patients with diffuse large B-cell lymphoma (DLBCL), 86 patients with follicular lymphoma (FL), and 53 patients with mantle cell lymphoma (MCL), and analyzed their prognostic relevance and effect on treatment response in these cohorts. Results: Positive Bcl-2 expression related strongly to lower rates of complete response (CR) after first-line treatment with Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in both DLBCL (p=0.001) and MCL (p=0.01). Bcl-2 was recognized as an independent predictor of poor overall survival (OS) (HR=2.9, p<0.001, and HR=3.7, p= 0.02 in DLBCL and MCL, respectively). Patients with positive expression of Bcl-6 were more likely to achieve CR after R-CHOP in both DLBCL (p=0.006) and FL (p=0.012). Bcl-6 positive expression was an independent indicator of a favorable OS (HR=0.3, p<0.001, and HR=0.4, p=0.04 in DLBCL and FL, respectively). An IHC score based on the expression of Bcl-2 and Bcl-6 in DLBCL accurately defined three risk groups with markedly different OS (p<0.001). This new score outweighed the International Prognostic Index (IPI) as a prognostic indicator (HR=3.2 vs 2.2, p<0.001). Conclusion: Bcl-2 and Bcl-6 protein expression detected by IHC can be reliably used to help predict treatment response and survival trends in a wide subset of B-NHLs. Funding Information: None to declare. Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: This study was approved by the local ethics committee.