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MDM2 as a predictor of prostate carcinoma outcome†
An analysis of Radiation Therapy Oncology Group protocol 8610
Article first published online: 8 JUL 2005
Copyright © 2005 American Cancer Society
Volume 104, Issue 5, pages 962–967, 1 September 2005
How to Cite
Khor, L.-Y., DeSilvio, M., Al-Saleem, T., Hammond, M. E., Grignon, D. J., Sause, W., Pilepich, M., Okunieff, P., Sandler, H. and Pollack, A. (2005), MDM2 as a predictor of prostate carcinoma outcome. Cancer, 104: 962–967. doi: 10.1002/cncr.21261
The contents of the current article are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute or the U.S. Department of Defense.
- Issue published online: 17 AUG 2005
- Article first published online: 8 JUL 2005
- Manuscript Accepted: 20 APR 2005
- Manuscript Revised: 25 MAR 2005
- Manuscript Received: 6 JAN 2005
- National Cancer Institute. Grant Number: CA-06927
- Department of Defense, US Army Medical Research. Grant Number: PC020427
- androgen deprivation;
- distant metastasis
The MDM2 oncoprotein promotes p53 degradation via ubiquitin, establishing negative feedback control of p53 and consequently affecting cell cycle arrest and apoptosis. The authors evaluated the association between MDM2 expression and local failure, distant metastasis (DM), cause-specific mortality, and overall mortality in men treated in Radiation Therapy Oncology Group 8610 with radiotherapy, with or without androgen deprivation.
Of the 456 eligible and analyzable patients (parent cohort), adequate archival diagnostic tissue specimens from 108 patients were available for MDM2 analysis (MDM2 cohort). Cox proportional hazards multivariate analysis (MVA) was used to determine the relation of MDM2 to the endpoints. MDM2 overexpression was manually classified as > 5% nuclear staining. An image analysis system was also used to quantify the proportion of tumor nuclei with MDM2 staining (ACIS index) and staining intensity.
Overexpression of MDM2 by manual counts was seen in 44% (n = 47) of the patients. In the manual count analysis, there was no significant relation between MDM2 overexpression and outcome. The ACIS index, using a cutoff point defined by the median value, ≤ 3% versus > 3%, was related to 5-year DM rates in univariate analyses (32.6% vs. 45.8%; P = 0.057) and MVA (P = 0.06). The intensity of MDM2 staining was not significant.
MDM2 expression quantified by image analysis was weakly associated with DM. The cohort examined was relatively small and with larger patient numbers, MDM2 overexpression may emerge as a more significant covariate. Cancer 2005. © 2005 American Cancer Society.