Expression of cysteine protease protein 32 in prostatic adenocarcinoma correlates with tumor grade.
BACKGROUND
Controlled cell death is mediated by apoptosis-specific genes, tumor suppressor genes, and oncogenes. The caspase family is a group of at least 15 known cysteine proteases that serve as initiator and effector molecules of the apoptosis pathway. On activation, caspases cause cell shrinkage, condensation of chromatin, fragmentation of DNA, and the formation of blebs in the cytoplasmic membrane.


OBJECTIVE
The patterns of cysteine protease protein (CCP) 32 (caspase-3) expression have been determined in normal human tissues and a variety of tumors, and have been shown to correlate with the outcome in breast cancer and linked to resistance to chemotherapy in other tumors. This study was performed to determine whether CPP32 is expressed in prostatic adenocarcinoma and to define its relationship with outcome variables.


METHODS
Formalin-fixed, paraffin-embedded radical prostatectomy specimens from 211 patients with prostatic adenocarcinoma were evaluated for CPP32 expression by immunohistochemistry. Hematoxylin-eosin-stained slides were reviewed, and tumors were graded based on the Gleason grading system. Tumors were scored for CPP32 expression semiquantitatively, based on the staining intensity and distribution patterns. These results were compared with Gleason grade and clinical and pathologic stages.


RESULTS
One hundred thirty-three (63%) of 211 cases showed high expression of CPP32, whereas expression was low in 78 (37%) cases. One hundred three (49%) of 211 cases had a high Gleason score (7 and above). Of 103 cases with a high Gleason score, 74 (72%) showed high CPP32 expression. Strong cytoplasmic staining for CPP32 in high-grade tumors was statistically significant (P =.01). Also, by linear regression analysis a significant correlation was seen between the Gleason score and the cytoplasmic CPP32 expression (P =.001). Expression of CPP32 did not correlate with either clinical stage (P =.28) or pathologic stage (P =.60); however, this study included very few patients with stage IV disease.


CONCLUSIONS
The correlation between CPP32 and high tumor grade suggests a CPP32-related high turnover rate in high-grade prostatic adenocarcinoma. Moreover, strong correlation with Gleason grade, a powerful predictor of disease progression and overall survival, suggests potential usefulness of CPP32 as a prognostic factor, especially in limited biopsy samples.
Anwar
Shahgul
S
Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY 12208, USA.
Ambros
Robert A
RA
Jennings
Timothy A
TA
Ross
Jeffrey S
JS
Beza
Anton
A
Mian
Badar
B
Nazeer
Tipu
T
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000473:pathology; D000368:Aged; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology
C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases