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


METHODS
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.
Khor
Li-Yan
LY
Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Desilvio
Michelle
M
Li
Rile
R
McDonnell
Timothy J
TJ
Hammond
M Elizabeth H
ME
Sause
William T
WT
Pilepich
Miljenko V
MV
Okunieff
Paul
P
Sandler
Howard M
HM
Pollack
Alan
A
D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006801:Humans; D008297:Male; D015337:Multicenter Studies as Topic; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
C494826:BAX protein, human; D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein