De novo nodal diffuse large B-cell lymphoma: identification of biologic prognostic factors.

BACKGROUND Diffuse large B-cell Lymphoma (DLBCL) represents the most frequent type of non-Hodgkin lymphoma (NHL). Although combination chemotherapy has improved the outcome, long-term cure is now possible for approximately 50% of all patients, making the search for parameters identifying patients at high risk particularly needed. The presence of bcl-2 gene rearrangement in de novo DLBCL suggests a possible follicle center cell origin and perhaps a distinct clinical behavior. This study investigated the frequency and prognostic significance of t(14;18) translocation and bcl-2 protein overexpression in a cohort of patients with de novo nodal DLBCL who where uniformly evaluated and treated. MATERIAL AND METHODS A total of 40 patients with de novo nodal DLBCL treated at National Cancer Institute (NCI), Cairo University were investigated. Formalin? fixed, paraffin-embedded sections were analyzed for: 1) bcl-2 gene rearrangement including major break point region (mbr) and minor cluster region (mcr) by polymerase chain reaction (PCR), and 2) bcl-2 protein expression by immunohistochemistry using Dako 124 clone. Results were correlated with the clinical features and subsequent clinical course. RESULTS Bcl-2 gene rearrangement was detected in 8 cases (20%), 2 cases at mbr, and 6 cases at mcr. Bcl-2 protein (>10%) was expressed in 24 cases (60%), irrespective of the presence of t(14;18) translocation. The t(14;18), and bcl-2 protein overexpression were more frequently associated with failure to achieve a complete response to therapy (p=0.008, and 0.04, respectively). DLBCL patients with t(14;18), and bcl-2 protein expression had a significantly reduced 5-year disease free survival (p=0.04, and 0.01, respectively). CONCLUSION The t(14;18) translocation, and bcl-2 protein expression define a group of DLBCL patients with a poor prognosis, and could be used to tailor treatment, and to identify candidates for therapeutic approaches. Geographic differences in t(14;18) may be related to the difference in distribution of bcl-2 breakpoints.