p53 Status and Prognosis of Locally Advanced Prostatic Adenocarcinoma: a Study Based on RTOG 8610

• Published in: JNCI : Journal of the National Cancer Institute 1997-01, Vol.89 (2), p.158-165
• Main Authors: Grignon, David J., Sarkar, Fazlul H., Forman, Jeffrey D., Caplan, Richard, Pajak, Thomas F., Lawton, Colleen A., Hammond, Elizabeth H., Pilepich, Miljenko V., Mesic, John, Fu, Karen K., Abrams, Ross A., Shipley, William U., Cox, James D.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - chemistry; Adenocarcinoma - pathology; Adenocarcinoma - secondary; Adenocarcinoma - therapy; Aged; Aged, 80 and over; Androgens; Antineoplastic Agents, Hormonal - therapeutic use; Biological and medical sciences; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Disease Progression; Disease-Free Survival; Flutamide - therapeutic use; Gene Expression Regulation, Neoplastic; Genes; Genes, p53 - genetics; Goserelin - therapeutic use; Humans; Male; Medical sciences; Middle Aged; Mutation; Nephrology. Urinary tract diseases; Prognosis; Prostate cancer; Prostatic Neoplasms - chemistry; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; Radiation; Radiotherapy, Adjuvant; Survival Analysis; Tumor Suppressor Protein p53 - metabolism; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/89.2.158

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 antip53 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