title: Increased bcl-2 protein levels in prostatic adenocarcinomas are not associated with rearrangements in the 2.8 kb major breakpoint region or with p53 protein accumulation.
abstract: bcl-2, an inhibitor of programmed cell death (apoptosis), is present in high levels in a subset of prostatic adenocarcinomas. In this study, 42 prostatic adenocarcinomas were analyzed to determine whether increased bcl-2 levels are associated with rearrangements in the 2.8-kb major breakpoint region, an association known to occur in certain follicular lymphomas featuring a t(14:18) translocation. Immunostaining for bcl-2 and p53 proteins was performed on formalin-fixed, paraffin-embedded tumor specimens using murine anti-human bcl-2 and p53 monoclonal antibodies in all 42 cases. Genomic DNA from paired frozen samples of each tumor was subjected to digestion with HindIII and EcoRI and the products analyzed on a Southern blot with a 2.8-kb-digoxigenin-labeled major breakpoint region probe. Comparisons between groups were evaluated with the Fisher exact test. Diffuse, strong cytoplasmic immunoreactivity for bcl-2 was present in the epithelial cells of tumor glands in 16 of 42 cases (38%), including 8 of 19 low grade (Gleason score 6 and below) and 8 of 23 high grade (Gleason score 7 and above) prostatic adenocarcinoma. Southern blotting demonstrated a normal 2.8-kb germline DNA fragment in every case, with no evidence of rearrangement. Nuclear p53 staining was present in 10 of 24 high grade and 0 of 18 low grade tumors (P < 0.001). Only four cases exhibited positivity for both bcl-2 and p53, and there was no association of bcl-2 positivity with co-expression of the p53 protein (P = 0.58). We conclude that aberrations in the function of either bcl-2 or p53 could possibly modify the apoptotic pathway resulting in the extended survival of tumor cells. Also, increased bcl-2 levels in prostatic adenocarcinomas occur in the absence of detectable rearrangements in the major breakpoint region.
authors.affiliation: Department of Pathology, Albany Medical College, NY 12208, USA.
authors.forename: B V
authors.initials: BV
authors.lastname: Kallakury
authors.forename: J
authors.initials: J
authors.lastname: Figge
authors.forename: B
authors.initials: B
authors.lastname: Leibovich
authors.forename: J
authors.initials: J
authors.lastname: Hwang
authors.forename: M
authors.initials: M
authors.lastname: Rifkin
authors.forename: R
authors.initials: R
authors.lastname: Kaufman
authors.forename: H L
authors.initials: HL
authors.lastname: Figge
authors.forename: T
authors.initials: T
authors.lastname: Nazeer
authors.forename: J S
authors.initials: JS
authors.lastname: Ross
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000235:genetics*; D015139:Blotting, Southern; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D013194:Staining and Labeling; D014178:Translocation, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53