Apoptosis and BCL-2 expression in prostate cancer: Significance in clinical outcome after brachytherapy

Purpose: Radiation induced apoptosis of prostate cancer cells may have ther apeutic and prognostic significance in patients treated with radiotherapy. We determined whether the ability of prostate tumor cells to undergo apopto sis has potential value for predicting the clinical response of patients wi th prostate cancer to brachytherapy. Materials and Methods: A total of 76 patients with clinical stages T1 to 2 disease who were not receiving adjuvant therapy underwent transperineal imp lantation with (125)iodine or (103)palladium seeds and biopsy 7 to 23 month s (median 12) after therapy. Nonresponders were classified using the Americ an Society for Therapeutic Radiology and Oncology criteria. The apoptotic i ndex was analyzed using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay in archived biopsy specim ens from 76 treated and 19 matched pretreatment control patients. Serial se ctions of prostatic tumors were also evaluated for the expression of bax an d bcl-2 proteins (apoptosis regulators) by immunohistochemical testing. Results: 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 compar ed with those with persistent malignancy (3.4% versus 1.8%, p = 0.02). In a ddition, 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). Conclusions: To our knowledge this is the first study to establish a correl ation of apoptosis induction and bcl-2 over expression with treatment outco me in patients with prostate cancer after brachytherapy. Our findings have significant clinical implications for identifying the value of the apoptoti c index and bcl-2 expression in prostatic tumors for predicting the therape utic response to brachytherapy.