Vergis, R., Corbishley, C. M., Thomas, K., Horwich, A., Huddart, R., Khoo, V., Eeles, R., Sydes, M. R., Cooper, C. S., Dearnaley, D., Parker, C. (2010) EXPRESSION OF Bcl-2, p53, AND MDM2 IN LOCALIZED PROSTATE CANCER WITH RESPECT TO THE OUTCOME OF RADICAL RADIOTHERAPY DOSE ESCALATION. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 78 (1). pp. 35-41. ISSN 0360-3016

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Abstract

Purpose: Established prognostic factors in localized prostate cancer explain only a moderate proportion of variation in outcome. We analyzed tumor expression of apoptotic markers with respect to outcome in men with localized prostate cancer in two randomized controlled trials of radiotherapy dose escalation. Methods and Materials: Between 1995 and 2001, 308 patients with localized prostate cancer received neoadjuvant androgen deprivation and radical radiotherapy at our institution in one of two dose-escalation trials. The biopsy specimens in 201 cases were used to make a biopsy tissue microarray. We evaluated tumor expression of Bcl-2, p53, and MDM2 by immunohistochemistry with respect to outcome. Results: Median follow-up was 7 years, and 5-year freedom from biochemical failure (FFBF) was 70.4% (95% CI, 63.5-76.3%). On univariate analysis, expression of Bcl-2 (p<0.001) and p53 (p=0.017), but not MDM2 (p=0.224), was significantly associated with FFBF. Expression of Bcl-2 remained significantly associated with FFBF (p=0.001) on multivariate analysis, independently of T stage, Gleason score, initial prostate-specific antigen level, and radiotherapy dose. Seven-year biochemical control was 61% vs. 41% (p=0.0122) for 74 Gy vs. 64 Gy, respectively, among patients with Bcl-2-positive tumors and 87% vs. 81% (p=0.423) for 74 Gy vs. 64 Gy, respectively, among patients with Bcl-2-negative tumors. There was no statistically significant interaction between dose and Bcl-2 expression. Conclusions: Bcl-2 expression was a significant, independent determinant of biochemical control after neoadjuvant androgen deprivation and radical radiotherapy for prostate cancer. These data generate the hypothesis that Bcl-2 expression could be used to inform the choice of radiotherapy dose in individual patients. (C) 2010 Elsevier Inc.

Item Type:	Article
Authors (ICR Faculty only):	Cooper, Colin and Dearnaley, David and Eeles, Rosalind and Horwich, Alan and Huddart, Robert and Parker, Chris and Khoo, Vincent
All Authors:	Vergis, R., Corbishley, C. M., Thomas, K., Horwich, A., Huddart, R., Khoo, V., Eeles, R., Sydes, M. R., Cooper, C. S., Dearnaley, D., Parker, C.
Uncontrolled Keywords:	Prostate; Apoptotic markers; Radiotherapy; Dose escalation;ANDROGEN DEPRIVATION; BAX EXPRESSION; RADIATION; CARCINOMA; APOPTOSIS; MEN; PROGNOSIS; MARKERS; CELLS; TRIAL
Funding Acknowledgement:	Cancer Research UK Section of Radiotherapy [CUK] [C46/A2131]; NCRI South of England Prostate Cancer Collaborative ; Grand Charity of Freemasons ; NHS ; Institute of Cancer Research ; NHS Executive
Funding Text:	Supported by the Institute of Cancer Research, the Cancer Research UK Section of Radiotherapy [CUK] grant number C46/A2131, the NCRI South of England Prostate Cancer Collaborative, and the Grand Charity of Freemasons. The authors acknowledge NHS funding to the NIHR Biomedical Research Centre. This work was undertaken in The Royal Marsden NHS Foundation Trust, which received a proportion of its funding from the NHS Executive; the views expressed in this publication are those of the authors and not necessarily those of the NHS Executive.
Research teams:	Clinical Units > Urology Unit Closed research groups > Clinical Academic Radiotherapy (Dr C Parker) ICR divisions > Radiotherapy and Imaging > Clinical Academic Radiotherapy (Dearnaley) ICR divisions > Radiotherapy and Imaging > Clinical Academic Radiotherapy (Huddart) ICR divisions > Genetics and Epidemiology > Oncogenetics ICR divisions > Radiotherapy and Imaging > Oncogenetics ICR divisions > Radiotherapy and Imaging > Clinical Academic Radiotherapy (Horwich) Closed research groups > Cell Transformation
Depositing User:	Users 10 not found.
Date Deposited:	29 Sep 2010 09:36
Last Modified:	22 Sep 2011 14:15
URI:	http://publications.icr.ac.uk/id/eprint/9870

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