bcl-2/bax ratio as a predictive marker for therapeutic response to radiotherapy in patients with prostate cancer

Timothy J. MacKey, Andrew Borkowski, Pradip Amin, Stephen C. Jacobs, Natasha Kyprianou

Research output: Contribution to journalArticlepeer-review

186 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1085-1090
Number of pages6
JournalUrology
Volume52
Issue number6
DOIs
StatePublished - Dec 1998
Externally publishedYes

Fingerprint

Dive into the research topics of 'bcl-2/bax ratio as a predictive marker for therapeutic response to radiotherapy in patients with prostate cancer'. Together they form a unique fingerprint.

Cite this