Causes and consequences of BCL2 overexpression in diffuse large B-cell lymphoma.
We investigated the frequency of bcl-2 protein overexpression in 80 diffuse large B-cell lymphoma (DLBCL) patients using both Western blotting and immunohistochemistry (IHC). Fifty-nine percent of the DLBCLs overexpressed bcl-2 protein by Western blot and 52% by IHC. The two methods usually gave concordant results (p=0.005), but 14 (21%) out of the 67 cases that were analyzed by both methods were positive by Western blot and negative by IHC, and 8 (12%) cases vice versa. Bcl-2 overexpression by IHC was associated with poor response to chemotherapy and poor survival, whereas these associations were not found when bcl-2 overexpression was determined by Western blotting. The molecular mechanisms leading to bcl-2 overexpression were evaluated by PCR, karyotype analysis, and comparative genomic hybridization (CGH). When studied by PCR and/or karyotype analysis, 12 (15%) of the 80 cases had translocation (14;18)(q32;q21). All 12 lymphomas with (14;18)(q32;q21) translocation had bcl-2 overexpression by Western blot as compared with 35 (51%) of the 68 lymphomas without translocation (p=0.001). Ten (29%) out of 34 cases that were analyzed by CGH showed amplification of chromosome 18 in which the BCL2 gene is located, and all cases showed bcl-2 overexpression by both Western blot and IHC. The results suggest that gene amplification and translocation are at least equally common mechanisms causing bcl-2 protein overexpression in DLBCL. Bcl-2 protein overexpression as determined by IHC is associated with poor response to chemotherapy and poor survival.
Rantanen
S
S
Department of Medical Genetics, Haartman Institute and Helsinki University Central Hospital, University of Helsinki, Finland. Sakari.Knuutila@helsinki.fi
Monni
O
O
Joensuu
H
H
Franssila
K
K
Knuutila
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D002648:Child; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000737:chemistry* / Q000175:diagnosis / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry* / Q000175:diagnosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism*; D012074:Remission Induction; D015996:Survival Rate
D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2