Objectives: Markers predictive of therapeutic response of prostatic tumors to radiotherapy may have major significance in optimizing effective treatment of prostate cancer. Because inherent cellular radioresistance plays a critical role in the failure of radiotherapy, in this study, we investigated whether there is a correlation between the ratio of two apoptosis regulators, bcl-2 (apoptosis suppressor) and bax (apoptosis inducer) in prostatic tumors and the clinical response to radiotherapy in patients with localized prostate cancer.
Methods: A retrospective review of records of 41 patients who underwent external beam radiotherapy for prostate cancer was conducted. On the basis of post-treatment prostate biopsy and prostate-specific antigen (PSA) criteria, the cancers of 20 patients were classified as radiation nonresponders and 21 as radiation responders. Immunohistochemical analysis was performed on paraffin-embedded prostate sections to determine the level of expression of the two apoptotic proteins, bcl-2 and bax, in tumor cells.
Results: bcl-2 immunoreactivity was significantly higher in prostatic tumors not responsive to radiotherapy (38.6+/-4.1), compared with the radiation responders (24.1+/-4.6) (P <0.001). Expression of bax protein was lower in nonresponders, but values were not significantly different from the responders. The resulting significantly higher bcl-2/bax ratio (P <0.01) correlated with poor therapeutic responsiveness of prostate cancer to radiotherapy (1.12+/-0.12 and 0.56+/-0.13, for nonresponders and responders, respectively). This correlation (r=0.67) was independent of age, PSA, and Gleason score.
Conclusions: These findings suggest that patients with an elevated bcl-2/bax ratio are at increased risk of their cancer failing to respond to radiotherapy. This study suggests a predictive value for the bcl-2/bax ratio as a potential molecular marker for predicting radioresistance of prostatic tumors.