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Expression of cysteine protease protein 32 in prostatic adenocarcinoma correlates with tumor grade
Shahgul Anwar1, Robert A Ambros, Timothy A Jennings
1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY 12208, USA.
Context:
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.
Objectives:
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.
Design:
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.
Conclusion:
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.
Insights
High expression of cysteine protease protein (CPP) 32, also known as caspase-3, correlates with high-grade prostatic adenocarcinoma. This finding suggests CPP32 may serve as a prognostic factor for prostate cancer progression.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Controlled cell death, or apoptosis, is regulated by specific genes including tumor suppressors and oncogenes.
- The caspase family, comprising at least 15 cysteine proteases, acts as key initiator and effector molecules in the apoptosis pathway.
- Activated caspases induce characteristic cellular changes like shrinkage, chromatin condensation, and DNA fragmentation.
Purpose of the Study:
- To investigate the expression patterns of cysteine protease protein 32 (CPP32), also known as caspase-3, in normal human tissues and various tumors.
- To determine if CPP32 is expressed in prostatic adenocarcinoma and to analyze its correlation with patient outcomes.
- To assess the relationship between CPP32 expression and established prognostic factors in prostate cancer.
Main Methods:
- Immunohistochemistry was employed to evaluate CPP32 expression in formalin-fixed, paraffin-embedded radical prostatectomy specimens from 211 patients.
- Tumors were graded using the Gleason grading system, and CPP32 expression was semiquantitatively scored based on staining intensity and distribution.
- Statistical analysis compared CPP32 expression levels with Gleason grade, clinical stage, and pathologic stage.
Main Results:
- High CPP32 expression was observed in 63% of the 211 prostatic adenocarcinoma cases.
- A statistically significant correlation was found between high CPP32 expression and high Gleason scores (≥7) (P = .01).
- Linear regression analysis revealed a significant correlation between Gleason score and cytoplasmic CPP32 expression (P = .001), but no significant correlation with clinical or pathologic stage.
Conclusions:
- The strong correlation between CPP32 expression and high tumor grade in prostatic adenocarcinoma suggests a potential role in high-grade tumor cell turnover.
- The significant association with Gleason grade, a key predictor of disease progression and survival, indicates CPP32's potential as a prognostic biomarker.
- CPP32 may be particularly useful as a prognostic factor in evaluating limited biopsy samples for prostate cancer.