PURPOSE: Bcl-2 is antiapoptotic, and its overexpression has been associated with resistance to androgen deprivation and poor outcome in some patients treated with radiotherapy. Bax is proapoptotic, regulating Bcl-2 through heterodimer formation. In a prior study, Bcl-2 and Bax were not related to outcome in locally advanced patients treated with radiotherapy or short-term androgen deprivation + radiotherapy (STAD+RT) on another Radiation Therapy Oncology Group trial (86-10). A follow-up investigation was carried out here in more contemporary high-risk men treated on Radiation Therapy Oncology Group 92-02 with STAD+RT or long-term AD+RT (LTAD+RT). EXPERIMENTAL DESIGN: Adequate tissue was available to be analyzed immunohistochemically in 502 patients for Bcl-2 and 343 patients for Bax. Univariate and multivariate analyses by Cox proportional hazards models were applied to end points of failure. RESULTS: Bcl-2 was positive in 45.6% cases, and Bax expression altered in 53.9% cases. Abnormal Bcl-2 was not related to any of the failure end points tested. Altered Bax expression was significantly associated with any failure (P = 0.023) and marginally with biochemical failure (P = 0.085). The combination of negative Bcl-2/normal Bax expression seemed more robust, being significantly related to reduced biochemical failure (P = 0.036) and any failure (P = 0.046). The predictive value of negative Bcl-2/normal Bax was most pronounced in those who received STAD+RT, as opposed to LTAD+RT. CONCLUSIONS:Normal Bax expression was associated with significantly more favorable outcome. The combination of negative Bcl-2 and normal Bax was more consistently significant, particularly when STAD+RT was the treatment administered. These data suggest that LTAD+RT should be used when either Bcl-2 or Bax is abnormally expressed.
RCT Entities:
PURPOSE:Bcl-2 is antiapoptotic, and its overexpression has been associated with resistance to androgen deprivation and poor outcome in some patients treated with radiotherapy. Bax is proapoptotic, regulating Bcl-2 through heterodimer formation. In a prior study, Bcl-2 and Bax were not related to outcome in locally advanced patients treated with radiotherapy or short-term androgen deprivation + radiotherapy (STAD+RT) on another Radiation Therapy Oncology Group trial (86-10). A follow-up investigation was carried out here in more contemporary high-risk men treated on Radiation Therapy Oncology Group 92-02 with STAD+RT or long-term AD+RT (LTAD+RT). EXPERIMENTAL DESIGN: Adequate tissue was available to be analyzed immunohistochemically in 502 patients for Bcl-2 and 343 patients for Bax. Univariate and multivariate analyses by Cox proportional hazards models were applied to end points of failure. RESULTS:Bcl-2 was positive in 45.6% cases, and Bax expression altered in 53.9% cases. Abnormal Bcl-2 was not related to any of the failure end points tested. Altered Bax expression was significantly associated with any failure (P = 0.023) and marginally with biochemical failure (P = 0.085). The combination of negative Bcl-2/normal Bax expression seemed more robust, being significantly related to reduced biochemical failure (P = 0.036) and any failure (P = 0.046). The predictive value of negative Bcl-2/normal Bax was most pronounced in those who received STAD+RT, as opposed to LTAD+RT. CONCLUSIONS: Normal Bax expression was associated with significantly more favorable outcome. The combination of negative Bcl-2 and normal Bax was more consistently significant, particularly when STAD+RT was the treatment administered. These data suggest that LTAD+RT should be used when either Bcl-2 or Bax is abnormally expressed.
Authors: M Krajewska; S Krajewski; J I Epstein; A Shabaik; J Sauvageot; K Song; S Kitada; J C Reed Journal: Am J Pathol Date: 1996-05 Impact factor: 4.307
Authors: Tobias Zellweger; Christoph Ninck; Martina Mirlacher; Matthias Annefeld; Andrew G Glass; Thomas C Gasser; Michael J Mihatsch; Edward P Gelmann; Lukas Bubendorf Journal: Prostate Date: 2003-04-01 Impact factor: 4.104
Authors: M Colombel; F Symmans; S Gil; K M O'Toole; D Chopin; M Benson; C A Olsson; S Korsmeyer; R Buttyan Journal: Am J Pathol Date: 1993-08 Impact factor: 4.307
Authors: Alan Pollack; Didier Cowen; Patricia Troncoso; Gunar K Zagars; Andrew C von Eschenbach; Marvin L Meistrich; Timothy McDonnell Journal: Cancer Date: 2003-04-01 Impact factor: 6.860
Authors: Benjamin D Zeitlin; Aaron C Spalding; Marcia S Campos; Naoki Ashimori; Zhihong Dong; Shaomeng Wang; Theodore S Lawrence; Jacques E Nör Journal: Int J Radiat Oncol Biol Phys Date: 2010-08-01 Impact factor: 7.038
Authors: Alan Pollack; James J Dignam; Dayssy A Diaz; Qian Wu; Radka Stoyanova; Kyounghwa Bae; Adam P Dicker; Howard Sandler; Gerald E Hanks; Felix Y Feng Journal: Clin Cancer Res Date: 2014-10-07 Impact factor: 12.531
Authors: Nicholas G Zaorsky; Nitin Ohri; Timothy N Showalter; Adam P Dicker; Robert B Den Journal: Cancer Treat Rev Date: 2013-03-01 Impact factor: 12.111
Authors: Mohammad Aminur Rahman; A R M Ruhul Amin; Dongsheng Wang; Lydia Koenig; Sreenivas Nannapaneni; Zhengjia Chen; Zhibo Wang; Gabriel Sica; Xingming Deng; Zhuo Georgia Chen; Dong M Shin Journal: Clin Cancer Res Date: 2013-05-29 Impact factor: 12.531
Authors: F McCarthy; A Fletcher; N Dennis; C Cummings; H O'Donnell; J Clark; P Flohr; R Vergis; S Jhavar; C Parker; C S Cooper Journal: J Clin Pathol Date: 2009-08 Impact factor: 3.411