Prognostic value of abnormal p53 expression in locally advanced prostate cancer treated with androgen deprivation and radiotherapy: a study based on RTOG 9202.
OBJECTIVE
The goal of this study was to verify the significance of p53 as a prognostic factor in Radiation Therapy Oncology Group 9202, which compared short-term androgen deprivation (STAD) with radiation therapy (RT) to long-term androgen deprivation + RT in men with locally advanced prostate cancer (Pca).


METHODS
Tumor tissue was sufficient for p53 analysis in 777 cases. p53 status was determined by immunohistochemistry. Abnormal p53 expression was defined as 20% or more tumor cells with positive nuclei. Univariate and multivariate Cox proportional hazards models were used to evaluate the relationships of p53 status to patient outcomes.


RESULTS
Abnormal p53 was detected in 168 of 777 (21.6%) cases, and was significantly associated with cause-specific mortality (adjusted hazard ratio [HR] = 1.89; 95% confidence interval (CI) 1.14 - 3.14; p = 0.014) and distant metastasis (adjusted HR = 1.72; 95% CI 1.13-2.62; p = 0.013). When patients were divided into subgroups according to assigned treatment, only the subgroup of patients who underwent STAD + RT showed significant correlation between p53 status and cause-specific mortality (adjusted HR = 2.43; 95% CI = 1.32-4.49; p = 0.0044). When patients were divided into subgroups according to p53 status, only the subgroup of patients with abnormal p53 showed significant association between assigned treatment and cause-specific mortality (adjusted HR = 3.81; 95% CI 1.40-10.37; p = 0.0087).


CONCLUSIONS
Abnormal p53 is a significant prognostic factor for patients with prostate cancer who undergo short-term androgen deprivation and radiotherapy. Long-term androgen deprivation may significantly improve the cause-specific survival for those with abnormal p53.
Che
Mingxin
M
Department of Pathology, Wayne State University, Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA. mingxinche@hotmail.com
DeSilvio
Michelle
M
Pollack
Alan
A
Grignon
David J
DJ
Venkatesan
Varagur Mohan
VM
Hanks
Gerald E
GE
Sandler
Howard M
HM
D000368:Aged; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002423:Cause of Death; D003131:Combined Modality Therapy / Q000379:methods; D006801:Humans; D008297:Male; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000726:Androgen Antagonists; D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53
Cancer Res. 2000 Mar 15;60(6):1585-94
10749127
J Urol. 1999 Jul;162(1):12-6; discussion 16-7
10379729
Int J Radiat Oncol Biol Phys. 2000 Dec 1;48(5):1507-12
11121656
Am J Clin Pathol. 2001 Sep;116(3):360-8
11554164
Int J Radiat Oncol Biol Phys. 2002 Jul 1;53(3):574-80
12062599
J Clin Oncol. 2003 Apr 1;21(7):1238-48
12663710
J Clin Oncol. 2003 Nov 1;21(21):3972-8
14581419
Mol Cell Biol. 1988 Feb;8(2):531-9
2832726
Oncogene. 1990 Jun;5(6):893-9
1694291
Jpn J Cancer Res. 1992 Jan;83(1):101-6
1544866
J Natl Cancer Inst. 1992 Jun 3;84(11):883-7
1350643
Cancer Res. 1993 Jul 15;53(14):3369-73
8324747
J Natl Cancer Inst. 1993 Oct 20;85(20):1657-69
7692074
Int J Cancer. 1994 May 15;57(4):498-503
7910151
Jpn J Cancer Res. 1994 Aug;85(8):825-30
7928628
Hum Pathol. 1995 Jan;26(1):106-9
7821906
Int J Radiat Oncol Biol Phys. 1996 Jul 15;35(5):885-9
8751397
Eur Urol. 1996;30(1):65-72
8854070
J Natl Cancer Inst. 1997 Jan 15;89(2):158-65
8998185
Int J Cancer. 1997 Jun 20;74(3):346-58
9221816
Urology. 1998 Feb;51(2):346-51
9495727
J Clin Oncol. 1998 Sep;16(9):3158-68
9738588
Clin Cancer Res. 1995 Oct;1(10):1111-8
9815901
Clin Cancer Res. 1997 Aug;3(8):1389-97
9815823
Clin Cancer Res. 2000 Nov;6(11):4402-8
11106260