MDM2 and Ki-67 Predict for Distant Metastasis and Mortality in Men Treated With Radiotherapy and Androgen Deprivation for Prostate Cancer: RTOG 92-02

Li-Yan Khor; Kyounghwa Bae; Rebecca Paulus; Tahseen Al-Saleem; M. Elizabeth Hammond; David J Grignon; Mingxin Che; Varagur Venkatesan; Roger W Byhardt; Marvin Rotman; Gerald E Hanks; Howard M Sandler; Alan Pollack

doi:10.1200/JCO.2008.19.8267

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MDM2 and Ki-67 Predict for Distant Metastasis and Mortality in Men Treated With Radiotherapy and Androgen Deprivation for Prostate Cancer: RTOG 92-02

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MDM2 and Ki-67 Predict for Distant Metastasis and Mortality in Men Treated With Radiotherapy and Androgen Deprivation for Prostate Cancer: RTOG 92-02

Li-Yan Khor, Kyounghwa Bae, Rebecca Paulus, Tahseen Al-Saleem, M. Elizabeth Hammond, David J Grignon, Mingxin Che, Varagur Venkatesan, Roger W Byhardt, Marvin Rotman, …

Journal of clinical oncology, Vol.27(19), pp.3177-3184

2009-07-01

DOI: https://doi.org/10.1200/JCO.2008.19.8267

PMCID: PMC2716939

PMID: 19470936

Abstract

Purpose MDM2 regulates p53, which controls cell cycle arrest and apoptosis. Both proteins, along with Ki-67, which is an established strong determinant of metastasis, have shown promise in predicting the outcome of men treated with radiation therapy (RT) with or without short-term androgen deprivation (STAD). This report compares the utility of abnormal expression of these biomarkers in estimating progression in a cohort of men treated on RTOG 92-02. Patients and Methods Adequate tissue for immunohistochemistry was available for p53, Ki-67, and MDM2 analyses in 478 patient cases. The percentage of tumor nuclei staining positive (PSP) was quantified manually or by image analysis, and the per-sample mean intensity score (MIS) was quantified by image analysis. Cox regression models were used to estimate overall mortality (OM), and Fine and Gray's regressions were applied to the end points of distant metastasis (DM) and cause-specific mortality (CSM). Results In multivariate analyses that adjusted for all markers and treatment covariates, MDM2 overexpression was significantly related to DM (P = .02) and OM (P = .003), and Ki-67 overexpression was significantly related to DM (P < .0001), CSM (P = .0007), and OM (P = .01). P53 overexpression was significantly related to OM (P = .02). When considered in combination, the overexpression of both Ki-67 and MDM2 at high levels was associated with significantly increased failure rates for all end points (P < .001 for DM, CSM, and OM). Conclusion Combined MDM2 and Ki-67 expression levels were independently related to distant metastasis and mortality and, if validated, could be considered for risk stratification of patients with prostate cancer in clinical trials.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.25 Molecular & Cell Biology - Cancer, Autophagy & Apoptosis; 1.25.656 P53
Web Of Science research areas: Oncology
ESI research areas: Clinical Medicine

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Title: MDM2 and Ki-67 Predict for Distant Metastasis and Mortality in Men Treated With Radiotherapy and Androgen Deprivation for Prostate Cancer: RTOG 92-02
Creators: Li-Yan Khor - From the Department of Pathology, Drexel University College of Medicine; Department of Statistics, Radiation Therapy Oncology Group, American College of Radiology; and Departments of Pathology and of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA; Department of Pathology, LDS Hospital, Intermountain Health Care, Salt Lake City, UT; Department of Pathology, Indiana University, Indianapolis, IN; Department of Anatomic Pathology, Quest Diagnostics Incorporated, Schaumberg, IL; Radiation
Kyounghwa Bae - From the Department of Pathology, Drexel University College of Medicine; Department of Statistics, Radiation Therapy Oncology Group, American College of Radiology; and Departments of Pathology and of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA; Department of Pathology, LDS Hospital, Intermountain Health Care, Salt Lake City, UT; Department of Pathology, Indiana University, Indianapolis, IN; Department of Anatomic Pathology, Quest Diagnostics Incorporated, Schaumberg, IL; Radiation
Rebecca Paulus - From the Department of Pathology, Drexel University College of Medicine; Department of Statistics, Radiation Therapy Oncology Group, American College of Radiology; and Departments of Pathology and of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA; Department of Pathology, LDS Hospital, Intermountain Health Care, Salt Lake City, UT; Department of Pathology, Indiana University, Indianapolis, IN; Department of Anatomic Pathology, Quest Diagnostics Incorporated, Schaumberg, IL; Radiation
Tahseen Al-Saleem - From the Department of Pathology, Drexel University College of Medicine; Department of Statistics, Radiation Therapy Oncology Group, American College of Radiology; and Departments of Pathology and of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA; Department of Pathology, LDS Hospital, Intermountain Health Care, Salt Lake City, UT; Department of Pathology, Indiana University, Indianapolis, IN; Department of Anatomic Pathology, Quest Diagnostics Incorporated, Schaumberg, IL; Radiation
M. Elizabeth Hammond - From the Department of Pathology, Drexel University College of Medicine; Department of Statistics, Radiation Therapy Oncology Group, American College of Radiology; and Departments of Pathology and of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA; Department of Pathology, LDS Hospital, Intermountain Health Care, Salt Lake City, UT; Department of Pathology, Indiana University, Indianapolis, IN; Department of Anatomic Pathology, Quest Diagnostics Incorporated, Schaumberg, IL; Radiation
David J Grignon - From the Department of Pathology, Drexel University College of Medicine; Department of Statistics, Radiation Therapy Oncology Group, American College of Radiology; and Departments of Pathology and of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA; Department of Pathology, LDS Hospital, Intermountain Health Care, Salt Lake City, UT; Department of Pathology, Indiana University, Indianapolis, IN; Department of Anatomic Pathology, Quest Diagnostics Incorporated, Schaumberg, IL; Radiation
Mingxin Che - From the Department of Pathology, Drexel University College of Medicine; Department of Statistics, Radiation Therapy Oncology Group, American College of Radiology; and Departments of Pathology and of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA; Department of Pathology, LDS Hospital, Intermountain Health Care, Salt Lake City, UT; Department of Pathology, Indiana University, Indianapolis, IN; Department of Anatomic Pathology, Quest Diagnostics Incorporated, Schaumberg, IL; Radiation
Varagur Venkatesan - From the Department of Pathology, Drexel University College of Medicine; Department of Statistics, Radiation Therapy Oncology Group, American College of Radiology; and Departments of Pathology and of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA; Department of Pathology, LDS Hospital, Intermountain Health Care, Salt Lake City, UT; Department of Pathology, Indiana University, Indianapolis, IN; Department of Anatomic Pathology, Quest Diagnostics Incorporated, Schaumberg, IL; Radiation
Roger W Byhardt - From the Department of Pathology, Drexel University College of Medicine; Department of Statistics, Radiation Therapy Oncology Group, American College of Radiology; and Departments of Pathology and of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA; Department of Pathology, LDS Hospital, Intermountain Health Care, Salt Lake City, UT; Department of Pathology, Indiana University, Indianapolis, IN; Department of Anatomic Pathology, Quest Diagnostics Incorporated, Schaumberg, IL; Radiation
Marvin Rotman - From the Department of Pathology, Drexel University College of Medicine; Department of Statistics, Radiation Therapy Oncology Group, American College of Radiology; and Departments of Pathology and of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA; Department of Pathology, LDS Hospital, Intermountain Health Care, Salt Lake City, UT; Department of Pathology, Indiana University, Indianapolis, IN; Department of Anatomic Pathology, Quest Diagnostics Incorporated, Schaumberg, IL; Radiation
Gerald E Hanks - From the Department of Pathology, Drexel University College of Medicine; Department of Statistics, Radiation Therapy Oncology Group, American College of Radiology; and Departments of Pathology and of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA; Department of Pathology, LDS Hospital, Intermountain Health Care, Salt Lake City, UT; Department of Pathology, Indiana University, Indianapolis, IN; Department of Anatomic Pathology, Quest Diagnostics Incorporated, Schaumberg, IL; Radiation
Howard M Sandler - From the Department of Pathology, Drexel University College of Medicine; Department of Statistics, Radiation Therapy Oncology Group, American College of Radiology; and Departments of Pathology and of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA; Department of Pathology, LDS Hospital, Intermountain Health Care, Salt Lake City, UT; Department of Pathology, Indiana University, Indianapolis, IN; Department of Anatomic Pathology, Quest Diagnostics Incorporated, Schaumberg, IL; Radiation
Alan Pollack - From the Department of Pathology, Drexel University College of Medicine; Department of Statistics, Radiation Therapy Oncology Group, American College of Radiology; and Departments of Pathology and of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA; Department of Pathology, LDS Hospital, Intermountain Health Care, Salt Lake City, UT; Department of Pathology, Indiana University, Indianapolis, IN; Department of Anatomic Pathology, Quest Diagnostics Incorporated, Schaumberg, IL; Radiation
Publication Details: Journal of clinical oncology, Vol.27(19), pp.3177-3184
Academic Unit: Leadership Department; Miller School of Medicine; UMMG Dept of Radiation Oncology
Language: English
Resource Type: Journal article
PMID: 19470936
PMCID: PMC2716939
Record Identifier: 991031560001402976