Characterization of genetic lesions in apoptosis-regulating and proliferation control genes in diffuse large B-cell non-Hodgkin's lymphoma.
BACKGROUND
This study was conducted to analyze the frequency, expression patterns, and the impact of individual proteins BCL2, BCL6, and p53 on overall survival (OS) in adult, diffuse large B-cell lymphoma (DLBCL) patients. BCL2 gene was further investigated for potential alterations at the DNA level and correlated with OS.


METHODS
A total of 117 adult well-characterized DLBCL cases were included. The panel of antibodies comprised CD45, CD20, CD79a, CD3, BCL2, BCL6, and p53. PCR was also employed to correlate the events at the DNA level in BCL2.


RESULTS
The mean and median ages were 47.74 and 49 with a M:F ratio of 2.07:1. The incidence of BCL2, BCL6, and p53 expression was observed in 64.10%, 37.60%, and 52.13% of cases, respectively. Amplifiable quality DNA was available from 90 cases. BCL2/IGH translocation was found in 35/90 patients (38.88%) with 24 cases showing BCL2 (MBR)/IGH and 11 cases BCL2 (mcr)/IGH translocation. No association between BCL2 overexpression and BCL2 /IGH translocation was seen. Clinical data were available for 52 patients treated by CHOP therapy. It was found that patients with p53 overexpression had decreased overall survival (P = 0.0004) whereas BCL2, BCL6 expression, and BCL2/IGH translocation had no impact on overall survival.


CONCLUSIONS
Our data suggest that simple p53 protein expression by IHC at the time of diagnosis may help to identify high-risk patients, who may benefit with more aggressive and newer treatments in addition to standard CHOP.
Pervez
Shahid
S
Department of Pathology and Microbiology, Aga Khan University Medical Centre, Karachi, Pakistan.
Nasir
Muhammd I
MI
Moatter
Tariq
T
Ahsan
Adeeb
A
Haq
Amna
A
Siddiqui
Tariq
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis; D049109:Cell Proliferation; D003520:Cyclophosphamide; D004268:DNA-Binding Proteins / Q000235:genetics*; D004317:Doxorubicin; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D050438:Genes, Immunoglobulin Heavy Chain; D019254:Genes, bcl-2; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011241:Prednisone; D051560:Proto-Oncogene Proteins c-bcl-6; D014178:Translocation, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014750:Vincristine; D055815:Young Adult
D015703:Antigens, CD; C084103:BCL6 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D016159:Tumor Suppressor Protein p53; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone