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.
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.
Authors: Li-Yan Khor; Michelle Desilvio; Rile Li; Timothy J McDonnell; M Elizabeth H Hammond; William T Sause; Miljenko V Pilepich; Paul Okunieff; Howard M Sandler; Alan Pollack Journal: Int J Radiat Oncol Biol Phys Date: 2006-07-11 Impact factor: 7.038
Authors: Li Yan Khor; Jennifer Moughan; Tahseen Al-Saleem; Elizabeth H Hammond; Varagur Venkatesan; Seth A Rosenthal; Mark A Ritter; Howard M Sandler; Gerald E Hanks; William U Shipley; Alan Pollack Journal: Clin Cancer Res Date: 2007-06-15 Impact factor: 12.531
Authors: Robert L Grubb; Jianghong Deng; Peter A Pinto; James L Mohler; Arul Chinnaiyan; Mark Rubin; W Marston Linehan; Lance A Liotta; Emanuel F Petricoin; Julia D Wulfkuhle Journal: J Proteome Res Date: 2009-06 Impact factor: 4.466