Bcl-2 and bax expression and prostate cancer outcome in men treated with radiotherapy in Radiation Therapy Oncology Group protocol 86-10

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

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Purpose: Bcl-2 and bax are proteins with opposing roles in apoptosis regulation; yet abnormal expression of either has been associated with failure after radiotherapy (RT). In this study we examined bcl-2 and bax expression as predictive markers in men treated with radiotherapy ± androgen deprivation on Radiation Therapy Oncology Group (RTOG) protocol 86-10. Experimental Design: Suitable archival diagnostic tissue was obtained from 119 (26%) patients for bcl-2 analysis and 104 (23%) patients for bax analysis. Cox proportional hazards multivariate analysis was used to determine the relationship of abnormal bcl-2 and bax expression to the end points of local failure, distant metastasis, cause-specific mortality, and overall mortality. Bcl-2 overexpression was classified as any tumor cell cytoplasmic staining and altered bax expression was classified as greater or lesser cytoplasmic staining intensity of tumor cells as compared with adjacent normal prostate epithelium. Results: The study cohort exhibited bcl-2 overexpression in 26% (n = 30) of cases and abnormal bax expression in 47% (n = 49) of cases. A borderline significant relationship was observed between abnormal bax expression and higher Gleason score (p = 0.08). In univariate and multivariate analyses, there was no statistically significant relationship seen between abnormal bcl-2 or bax expression and outcome. Conclusions: Abnormal bcl-2 and bax expression were not related to any of the end points tested. The cohort examined was comprised of patients with locally advanced disease and it is possible that these markers may be of greater value in men with earlier-stage prostate cancer.

Original languageEnglish
Pages (from-to)25-30
Number of pages6
JournalInternational Journal of Radiation Oncology Biology Physics
Volume66
Issue number1
DOIs
StatePublished - Sep 1 2006
Externally publishedYes

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Radiation Oncology
radiation therapy
Prostatic Neoplasms
Radiotherapy
cancer
Multivariate Analysis
Staining and Labeling
bcl-2-Associated X Protein
Mortality
Neoplasm Grading
Androgens
Prostate
mortality
Neoplasms
Cohort Studies
Research Design
staining
Epithelium
markers
Apoptosis

Keywords

  • Androgen Deprivation
  • Bax
  • Bcl-2
  • Radiation Therapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Bcl-2 and bax expression and prostate cancer outcome in men treated with radiotherapy in Radiation Therapy Oncology Group protocol 86-10. / Khor, Li Yan; DeSilvio, Michelle; Li, Rile; McDonnell, Timothy J.; Hammond, M. Elizabeth H; Sause, William T.; Pilepich, Miljenko V.; Okunieff, Paul; Sandler, Howard M.; Pollack, Alan.

In: International Journal of Radiation Oncology Biology Physics, Vol. 66, No. 1, 01.09.2006, p. 25-30.

Research output: Contribution to journalArticle

Khor, Li Yan ; DeSilvio, Michelle ; Li, Rile ; McDonnell, Timothy J. ; Hammond, M. Elizabeth H ; Sause, William T. ; Pilepich, Miljenko V. ; Okunieff, Paul ; Sandler, Howard M. ; Pollack, Alan. / Bcl-2 and bax expression and prostate cancer outcome in men treated with radiotherapy in Radiation Therapy Oncology Group protocol 86-10. In: International Journal of Radiation Oncology Biology Physics. 2006 ; Vol. 66, No. 1. pp. 25-30.
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AU - DeSilvio, Michelle

AU - Li, Rile

AU - McDonnell, Timothy J.

AU - Hammond, M. Elizabeth H

AU - Sause, William T.

AU - Pilepich, Miljenko V.

AU - Okunieff, Paul

AU - Sandler, Howard M.

AU - Pollack, Alan

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N2 - Purpose: Bcl-2 and bax are proteins with opposing roles in apoptosis regulation; yet abnormal expression of either has been associated with failure after radiotherapy (RT). In this study we examined bcl-2 and bax expression as predictive markers in men treated with radiotherapy ± androgen deprivation on Radiation Therapy Oncology Group (RTOG) protocol 86-10. Experimental Design: Suitable archival diagnostic tissue was obtained from 119 (26%) patients for bcl-2 analysis and 104 (23%) patients for bax analysis. Cox proportional hazards multivariate analysis was used to determine the relationship of abnormal bcl-2 and bax expression to the end points of local failure, distant metastasis, cause-specific mortality, and overall mortality. Bcl-2 overexpression was classified as any tumor cell cytoplasmic staining and altered bax expression was classified as greater or lesser cytoplasmic staining intensity of tumor cells as compared with adjacent normal prostate epithelium. Results: The study cohort exhibited bcl-2 overexpression in 26% (n = 30) of cases and abnormal bax expression in 47% (n = 49) of cases. A borderline significant relationship was observed between abnormal bax expression and higher Gleason score (p = 0.08). In univariate and multivariate analyses, there was no statistically significant relationship seen between abnormal bcl-2 or bax expression and outcome. Conclusions: Abnormal bcl-2 and bax expression were not related to any of the end points tested. The cohort examined was comprised of patients with locally advanced disease and it is possible that these markers may be of greater value in men with earlier-stage prostate cancer.

AB - Purpose: Bcl-2 and bax are proteins with opposing roles in apoptosis regulation; yet abnormal expression of either has been associated with failure after radiotherapy (RT). In this study we examined bcl-2 and bax expression as predictive markers in men treated with radiotherapy ± androgen deprivation on Radiation Therapy Oncology Group (RTOG) protocol 86-10. Experimental Design: Suitable archival diagnostic tissue was obtained from 119 (26%) patients for bcl-2 analysis and 104 (23%) patients for bax analysis. Cox proportional hazards multivariate analysis was used to determine the relationship of abnormal bcl-2 and bax expression to the end points of local failure, distant metastasis, cause-specific mortality, and overall mortality. Bcl-2 overexpression was classified as any tumor cell cytoplasmic staining and altered bax expression was classified as greater or lesser cytoplasmic staining intensity of tumor cells as compared with adjacent normal prostate epithelium. Results: The study cohort exhibited bcl-2 overexpression in 26% (n = 30) of cases and abnormal bax expression in 47% (n = 49) of cases. A borderline significant relationship was observed between abnormal bax expression and higher Gleason score (p = 0.08). In univariate and multivariate analyses, there was no statistically significant relationship seen between abnormal bcl-2 or bax expression and outcome. Conclusions: Abnormal bcl-2 and bax expression were not related to any of the end points tested. The cohort examined was comprised of patients with locally advanced disease and it is possible that these markers may be of greater value in men with earlier-stage prostate cancer.

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