De novo nodal diffuse large b-cell lymphoma : Identification of biologic prognostic factors

Abstract EN

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.