APOPTOSIS AND BCL-2 EXPRESSION IN PROSTATE CANCER:

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Abstract
Radiation induced apoptosis of prostate cancer cells may have therapeutic and prognostic significance in patients treated with radiotherapy. We determined whether the ability of prostate tumor cells to undergo apoptosis has potential value for predicting the clinical response of patients with prostate cancer to brachytherapy. A total of 76 patients with clinical stages T1 to 2 disease who were not receiving adjuvant therapy underwent transperineal implantation with 125iodine or 103palladium seeds and biopsy 7 to 23 months (median 12) after therapy. Nonresponders were classified using the American Society for Therapeutic Radiology and Oncology criteria. The apoptotic index was analyzed using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay in archived biopsy specimens from 76 treated and 19 matched pretreatment control patients. Serial sections of prostatic tumors were also evaluated for the expression of bax and bcl-2 proteins (apoptosis regulators) by immunohistochemical testing. A significant increase in the apoptotic index was detected in post-brachytherapy compared with pretreatment prostate specimens (3.1% versus 2%, p <0.05), as well as in patients with negative biopsy at followup compared with those with persistent malignancy (3.4% versus 1.8%, p = 0.02). In addition, there was a significant elevation in bcl-2 expression in prostatic tissue in patients with treatment failure compared with responders (30.5% versus 13.1%, p <0.05). To our knowledge this is the first study to establish a correlation of apoptosis induction and bcl-2 over expression with treatment outcome in patients with prostate cancer after brachytherapy. Our findings have significant clinical implications for identifying the value of the apoptotic index and bcl-2 expression in prostatic tumors for predicting the therapeutic response to brachytherapy.

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