Bcl-2 and bax expression predict prostate cancer outcome in men treated with androgen deprivation and radiotherapy on radiation therapy oncology group protocol 92-02

Yan Khor Li, 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

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Abstract

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.

Original languageEnglish
Pages (from-to)3585-3590
Number of pages6
JournalClinical Cancer Research
Volume13
Issue number12
DOIs
StatePublished - Jun 15 2007
Externally publishedYes

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Radiation Oncology
Androgens
Prostatic Neoplasms
Radiotherapy
Proportional Hazards Models
Research Design
Multivariate Analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Bcl-2 and bax expression predict prostate cancer outcome in men treated with androgen deprivation and radiotherapy on radiation therapy oncology group protocol 92-02. / Li, Yan Khor; Moughan, Jennifer; Al-Saleem, Tahseen; Hammond, Elizabeth H.; Venkatesan, Varagur; Rosenthal, Seth A.; Ritter, Mark A.; Sandler, Howard M.; Hanks, Gerald E.; Shipley, William U.; Pollack, Alan.

In: Clinical Cancer Research, Vol. 13, No. 12, 15.06.2007, p. 3585-3590.

Research output: Contribution to journalArticle

Li, YK, Moughan, J, Al-Saleem, T, Hammond, EH, Venkatesan, V, Rosenthal, SA, Ritter, MA, Sandler, HM, Hanks, GE, Shipley, WU & Pollack, A 2007, 'Bcl-2 and bax expression predict prostate cancer outcome in men treated with androgen deprivation and radiotherapy on radiation therapy oncology group protocol 92-02', Clinical Cancer Research, vol. 13, no. 12, pp. 3585-3590. https://doi.org/10.1158/1078-0432.CCR-06-2972
Li, Yan Khor ; Moughan, Jennifer ; Al-Saleem, Tahseen ; Hammond, Elizabeth H. ; Venkatesan, Varagur ; Rosenthal, Seth A. ; Ritter, Mark A. ; Sandler, Howard M. ; Hanks, Gerald E. ; Shipley, William U. ; Pollack, Alan. / Bcl-2 and bax expression predict prostate cancer outcome in men treated with androgen deprivation and radiotherapy on radiation therapy oncology group protocol 92-02. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 12. pp. 3585-3590.
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abstract = "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.",
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T1 - Bcl-2 and bax expression predict prostate cancer outcome in men treated with androgen deprivation and radiotherapy on radiation therapy oncology group protocol 92-02

AU - Li, Yan Khor

AU - Moughan, Jennifer

AU - Al-Saleem, Tahseen

AU - Hammond, Elizabeth H.

AU - Venkatesan, Varagur

AU - Rosenthal, Seth A.

AU - Ritter, Mark A.

AU - Sandler, Howard M.

AU - Hanks, Gerald E.

AU - Shipley, William U.

AU - Pollack, Alan

PY - 2007/6/15

Y1 - 2007/6/15

N2 - 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.

AB - 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.

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