© 1997 by Oxford University Press
Journal Of The National Cancer Institute, Vol 89, 158-165, Copyright © 1997 by Oxford University Press
DJ Grignon, R Caplan, FH Sarkar, CA Lawton, EH Hammond, MV Pilepich, JD Forman, J Mesic, KK Fu, RA Abrams, TF Pajak, WU Shipley and JD Cox
BACKGROUND: The p53 tumor suppressor gene (also known as TP53) is one of
the most frequently mutated genes in human cancer. Several studies have
shown that p53 mutations are infrequent in prostate cancer and are
associated with advanced disease. PURPOSE: We assessed the prognostic value
of identifying abnormal p53 protein expression in the tumors of patients
with locally advanced prostate cancer who were treated with either
external-beam radiation therapy alone or total androgen blockade before and
during the radiation therapy. METHODS: The study population consisted of a
subset of patients entered in Radiation Therapy Oncology Group protocol
8610 ("a phase III trial of Zoladex and flutamide used as cytoreductive
agents in locally advanced carcinoma of the prostate treated with
definitive radiotherapy"). Immunohistochemical detection of abnormal p53
protein in pretreatment specimens (i.e., needle biopsies or transurethral
resections) was achieved by use of the monoclonal anti-p53 antibody DO7;
specimens in which 20% or more of the tumor cell nuclei showed positive
immunoreactivity were considered to have abnormal p53 protein expression.
Associations between p53 protein expression status and the time to local
progression, the incidence of distant metastases, progression-free
survival, and overall survival were evaluated in univariate (logrank test)
and multivariate (Cox proportional hazards model) analyses. Reported P
values are two-sided. RESULTS: One hundred twenty-nine (27%) of the 471
patients entered in the trial had sufficient tumor material for analysis.
Abnormal p53 protein expression was detected in the tumors of 23 (18%) of
these 129 patients. Statistically significant associations were found
between the presence of abnormal p53 protein expression and increased
incidence of distant metastases (P = .04), decreased progression-free
survival (P = .03), and decreased overall survival (P = .02); no
association was found between abnormal p53 protein expression and the time
to local progression (P = .58). These results were independent of the
Gleason score and clinical stage. A significant treatment interaction was
detected with respect to the development of distant metastases: Among
patients receiving both radiation therapy and hormone therapy, those with
tumors exhibiting abnormal p53 protein expression experienced a reduced
time to the development of distant metastases (P = .001); for patients
treated with radiation therapy alone, the time to distant metastases was
unrelated to p53 protein expression status (P = .91). CONCLUSIONS:
Determination of p53 protein expression status yield significant,
independent prognostic information concerning the development of distant
metastases, progression-free survival, and overall survival for patients
with locally advanced prostate cancer who are treated primarily with
radiation therapy. IMPLICATIONS: The interaction of radiation therapy plus
hormone therapy and abnormal p53 protein expression may provide a clinical
link to experimental evidence that radiation therapy and/or hormone therapy
act, at least in part, by the induction of apoptosis (a cell death program)
and suggests that this mechanism may be blocked in patients whose tumors
have p53 mutations.
ARTICLES
p53 status and prognosis of locally advanced prostatic adenocarcinoma: a study based on RTOG 8610
Wayne State University, Harper Hospital, Detroit, MI 48201, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. BICKERS and C. AUKIM-HASTIE New Molecular Biomarkers for the Prognosis and Management of Prostate Cancer - The Post PSA Era Anticancer Res, August 1, 2009; 29(8): 3289 - 3298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-Y. Khor, K. Bae, R. Paulus, T. Al-Saleem, M. E. Hammond, D. J. Grignon, M. Che, V. Venkatesan, R. W. Byhardt, M. Rotman, et al. MDM2 and Ki-67 Predict for Distant Metastasis and Mortality in Men Treated With Radiotherapy and Androgen Deprivation for Prostate Cancer: RTOG 92-02 J. Clin. Oncol., July 1, 2009; 27(19): 3177 - 3184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Hughes, A Murphy, C Martin, O Sheils, and J O'Leary Molecular pathology of prostate cancer J. Clin. Pathol., July 1, 2005; 58(7): 673 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. Pisters, C. A. Pettaway, P. Troncoso, T. J. McDonnell, L. C. Stephens, C. G. Wood, K.-A. Do, S. M. Brisbay, X. Wang, E. A. Hossan, et al. Evidence That Transfer of Functional p53 Protein Results in Increased Apoptosis in Prostate Cancer Clin. Cancer Res., April 15, 2004; 10(8): 2587 - 2593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Pollack, D.J. Grignon, K.H. Heydon, E.H. Hammond, C.A. Lawton, J.B. Mesic, K.K. Fu, A.T. Porter, R.A. Abrams, and W.U. Shipley Prostate Cancer DNA Ploidy and Response to Salvage Hormone Therapy After Radiotherapy With or Without Short-Term Total Androgen Blockade: An Analysis of RTOG 8610 J. Clin. Oncol., April 1, 2003; 21(7): 1238 - 1248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Taplin and S.-M. Ho The Endocrinology of Prostate Cancer J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3467 - 3477. [Full Text] [PDF]
|
|
|
|
 |
|
 D. I. Quinn, S. M. Henshall, D. R. Head, D. Golovsky, J. D. Wilson, P. C. Brenner, J. J. Turner, W. Delprado, J. F. Finlayson, P. D. Stricker, et al. Prognostic Significance of p53 Nuclear Accumulation in Localized Prostate Cancer Treated with Radical Prostatectomy Cancer Res., March 1, 2000; 60(6): 1585 - 1594. [Abstract] [Full Text]
|
|
|
|
|
|
W. K. Oh and P. W. Kantoff Treatment of Locally Advanced Prostate Cancer: Is Chemotherapy the Next Step? J. Clin. Oncol., November 1, 1999; 17(11): 3664 - 3675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ruijter, C. van de Kaa, G. Miller, D. Ruiter, F. Debruyne, and J. Schalken Molecular Genetics and Epidemiology of Prostate Carcinoma Endocr. Rev., February 1, 1999; 20(1): 22 - 45. [Abstract] [Full Text]
|
|