Survivin and Bcl-2 expression in prostatic adenocarcinomas.
BACKGROUND
Dysregulated cell proliferation caused by inhibitors of programmed cell death (apoptosis) contributes to tumor progression and spread. Aberrant expression of Bcl-2, the most notable inhibitor of apoptosis, has been well characterized in several human malignancies. Recent studies have described a novel apoptosis inhibitor, survivin, in human carcinomas, although its exact role remains to be characterized.


OBJECTIVE
The purpose of this study was to evaluate the immunohistochemical expression of Bcl-2 and survivin proteins in prostate cancer and to correlate the results with clinicopathologic variables.


METHODS
Formalin-fixed, paraffin-embedded tissue sections from 138 cases of prostatic adenocarcinomas (PACs) were immunostained by an automated method using specific antibodies against survivin and Bcl-2. Staining was semiquantitatively scored based on both intensity and distribution, and results were correlated with morphologic and prognostic variables.


RESULTS
Of the 138 PACs tested, 113 (82%) expressed survivin. We found no correlation between survivin expression and prognostic variables, including grade, stage, DNA content (ploidy), and recurrence. Bcl-2 expression was positive in 95 (69%) of these 138 cases and correlated with nondiploid DNA content. Fourteen (50%) of 28 nondiploid PACs expressed Bcl-2, compared to 17 (25%) of 68 diploid tumors (P =.02). A trend for association of Bcl-2 expression with tumor stage was noted as follows: 21 (39%) of 54 advanced-stage PACs expressed Bcl-2, in comparison with 20 (24%) of 84 low-stage tumors (P =.07). On univariate analysis, 25 (48%) of the 52 PACs that recurred expressed Bcl-2, as compared with 16 (19%) of the 86 nonrecurrent PACs (P <.001). No correlation was noted between survivin and Bcl-2 expression.


CONCLUSIONS
Survivin is expressed in a majority of PACs and is not a prognosis-related marker, but may be a potential target for apoptosis-based therapy. Overexpression of Bcl-2 correlates with other prognostic variables and predicts disease recurrence of PACs. These data also suggest that survivin and Bcl-2 may regulate cell proliferation and cell death through different mechanisms.
Kaur
Prabhjot
P
Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY 12208, USA.
Kallakury
Bhaskar S V
BS
Sheehan
Christine E
CE
Fisher
Hugh A G
HA
Kaufman
Ronald P
RP
Ross
Jeffrey S
JS
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology / Q000378:metabolism*; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin