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.


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).


CONCLUSIONS
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.
Abd El-Hameed
Amany
A
The Department of Pathology, NCI, Cairo University, Cairo.
D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D005260:Female; D019254:Genes, bcl-2 / Q000235:genetics*; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000401:mortality* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis* / Q000235:genetics; D014178:Translocation, Genetic
D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2