Burkitt Lymphoma ; classification ; genetics ; therapy ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; classification ; genetics ; therapy ; Lymphoma, B-Cell ; classification ; genetics ; therapy ; Lymphoma, Follicular ; classification ; genetics ; therapy ; Lymphoma, Large B-Cell, Diffuse ; classification ; genetics ; therapy ; Lymphoma, Mantle-Cell ; classification ; genetics ; therapy ; Prognosis

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in all countries and all age groups. DLBCL is potentially curable, and the outcome of patients with DLBCL has completely changed with the introduction of therapy involving the monoclonal antibody rituximab in combination with chemotherapy. Nonetheless, relapse is detected after treatment with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone in approximately 30% of patients. It has recently become clear that DLBCL represents a heterogeneous admixture of quite different entities. Gene expression profiling has uncovered DLBCL subtypes that have distinct clinical behaviors and prognoses; however, incorporation of this information into treatment algorithms awaits further investigation. Future approaches to DLBCL treatment will use this new genetic information to identify potential biomarkers for prognosis and targets for treatment.
Algorithms ; Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Gene Expression Profiling ; Humans ; Lymphoma, Large B-Cell, Diffuse/classification/genetics/*therapy ; Salvage Therapy ; Stem Cell Transplantation

<b>OBJECTIVEb>To evaluate the molecular mechanism and prognostication of bcl-2 protein expression in different subgroups of diffuse large B-cell lymphoma(DLBCL) in Guangxi Zhuang Autonomous Region, China.

<b>METHODSb>Immunohistochemical stains for CD10, bcl-6, MUM-1, bcl-2 and NF-κB were performed in 214 cases of DLBCL. The Hans immunologic classification was applied to classify DLBCL into GCB and non-GCB subgroups. Using a dual-probe fluorescence in-situ hybridization (FISH) assay, IgH/bcl-2 gene translocation and bcl-2 amplification were analyzed.

<b>RESULTSb>In 214 cases of DLBCL, 30.8% (66/214) of cases were GCB and 69.2% (148/214) were non-GCB. Twenty-seven point three percent (18/66) of GCB subgroups and 59.5% (88/148) of non-GCB subgroups had bcl-2 protein expression, with a significant difference (P < 0.01). IgH/bcl-2 translocation was positive in 3.7% (8/214) of cases, even majority of them (6/8) was found in GCB subgroup, while represented only 9.1% of GCB case. There was a significant difference (P = 0.02) in bcl-2 gene amplification between GCB (27/66, 40.9%) and non-GCB subgroup (86/148, 58.1%). Among non-GCB cases, the expression of bcl-2 was correlated with that of NF-κB expression and bcl-2 gene amplification (r = 0.216 and 0.219, respectively, P < 0.05). No similar correlation was observed in GCB cases. The overall survival time of bcl-2-positive patients (31.4 ± 3.8) months was shorter than that of bcl-2-negative patients (40.2 ± 4.2) months. In conjunction with immunophenotypes and clinical stages, the bcl-2 positive patients had a 1.89 times higher risk than that of the bcl-2 negative patients.

<b>CONCLUSIONSb>Majority of the cases were prognostically unfavorable non-GCB subgroups among DLBCL, which were characterized by high frequency of bcl-2 gene amplification and low frequency of IgH/bcl-2 translocation. The anti-apoptotic gene bcl-2 was frequently expressed in non-GCB subgroups and closely related to the gene amplification and NF-κB activation. bcl-2 positive patients had more short overall survival times, would face significant higher risk of death, these results suggested that bcl-2 could be a prognostic marker independent to clinical staging and immunophenotyping.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Genes, bcl-2 ; Humans ; Immunoglobulin Heavy Chains ; genetics ; In Situ Hybridization, Fluorescence ; Lymphoma, Large B-Cell, Diffuse ; classification ; drug therapy ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; NF-kappa B ; metabolism ; Prednisone ; therapeutic use ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Survival Rate ; Translocation, Genetic ; Vincristine ; therapeutic use ; Young Adult