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Molecular markers of outcome after radiotherapy in patients with prostate carcinoma
Ki-67, bcl-2, bax, and bcl-x
Version of Record online: 18 MAR 2003
Copyright © 2003 American Cancer Society
Volume 97, Issue 7, pages 1630–1638, 1 April 2003
How to Cite
Pollack, A., Cowen, D., Troncoso, P., Zagars, G. K., von Eschenbach, A. C., Meistrich, M. L. and McDonnell, T. (2003), Molecular markers of outcome after radiotherapy in patients with prostate carcinoma. Cancer, 97: 1630–1638. doi: 10.1002/cncr.11230
- Issue online: 18 MAR 2003
- Version of Record online: 18 MAR 2003
- Manuscript Accepted: 26 NOV 2002
- Manuscript Revised: 25 SEP 2002
- Manuscript Received: 19 JUN 2002
- National Cancer Institute, U.S. Department of Health and Human Services. Grant Numbers: PO1 CA78778, P50 CA90270, CA06294, CA16672
- Department of Defense Grant. Grant Number: DAMD 17-98-1-8483
- American Cancer Society Grant. Grant Number: RSG-CDD 101054
- Prostate Cancer Research Program at the University of Texas M. D. Anderson Cancer Center
- prostate carcinoma;
- prostate specific antigen;
Abnormal expression of key proteins of the apoptotic pathway has been associated with poor prognosis, although there have been few studies of these correlations in patients with prostate carcinoma who are treated with radiotherapy. The current study examined the association between expression levels of Ki-67, bcl-2, bax, and bcl-x in pretreatment biopsy specimens and patient outcome after definitive radiotherapy alone.
Archival pretreatment prostate biopsy tumor tissue was retrieved from 106 patients with Stage T1–T3 prostate carcinoma who were treated at the University of Texas M. D. Anderson Cancer Center with external beam radiotherapy between 1987 and 1993. Expression levels of Ki-67 (MIB-1 staining; n = 106 patients), bcl-2 (n = 77 patients), bax (n = 70 patients), and bcl-x (both long and short splice variants; n = 72 patients) were determined by immunohistochemical staining. The Ki-67 labeling index (Ki67-LI) was available for all patients and was derived from the percentage of Ki-67 positive cells. Biochemical failure after radiotherapy was defined as three consecutive rises in prostate specific antigen level on follow-up. The median follow-up was 62 months.
High Ki67-LI (> 3.5%) expression was observed in 33% of patients, overexpression of bcl-2 was observed in 16% of patients, altered bax expression was observed in 23% of patients, and altered bcl-x expression was observed in 53% of patients. There was no correlation found between the biomarkers. Kaplan–Meier survival estimates of freedom from biochemical failure (bNED) and the log-rank test revealed significantly lower rates in association with high Ki67-LI, positive bcl-2, and altered bax staining. No correlation was observed between bcl-x staining and bNED. Cox proportional hazards multivariate analysis confirmed that bcl-2 and bax were independent of pretreatment PSA level, Gleason score, disease stage, and Ki67-LI in predicting bNED.
Abnormalities in the expression levels of bcl-2 and bax were associated with increased failure after patients were treated for prostate carcinoma with external beam radiotherapy. These biomarkers appeared to be useful in categorizing patient risk further, beyond Ki-67 staining and conventional clinical prognostic factors. Cancer 2003;97:1630–8. © 2003 American Cancer Society.