p53 Expression and Clinical Outcome in Prostate Cancer

Abstract

Abnormally high levels of expression of p53 protein are found in many human cancers. In most cases increased expression is associated with point mutations in one allele of the p53 gene and loss of the other allele. Accumulation of the protein product can be detected by immunohistochemistry. p53 protein expression in 68 men with prostate cancer, followed up for at least 8 years or until death, was assessed by immunohistochemistry. The aim of the study was to determine the association between p53 protein expression, cell cycling and clinical outcome. Nine (13%) of 68 tumours stained positively for p53; all 9 tumours were category T3 or T4. p53 positive tumours had a significantly greater Gleason score than p53 negative tumours. Eight of the 9 p53 positive tumours had > 10% cells in G2 + mitosis, compared with 61% of p53 negative tumours. All 17 patients with p53 positive tumours available for follow-up progressed clinically, compared with 28 of 38 patients (74%) with p53 negative tumours. The median time to progression was 12 months in p53 positive tumours and 24 months in p53 negative tumours. Median survival in p53 positive tumours was 40 months, compared with 76 months in p53 negative tumours. This study demonstrates that overexpression of p53 in a small population of prostate cancers is associated with a poor prognosis in terms of progression and survival.

p53 Alteration and Chromosomal Instability in Prostatic High-Grade Intraepithelial Neoplasia and Concurrent Carcinoma: Analysis by Immunohistochemistry, Interphase In Situ Hybridization, and Sequencing of Laser-Captured Microdissected Specimens

“…In five of seven p53ϩ cases, pathological examination showed extraprostatic extension, and that finding was seen in 10 patients out of 28 of the p53-negative cases (P ϭ .1). Focal cytoplasmic staining was seen in four cases (Patients 3,5,11 and 20) in the Pca and HPIN foci and was counted as negative. Focal (scattered cells) p53 basal staining was seen in about 30% of the cases in the hyperplastic foci but was found very rarely in HPIN foci.…”

Molecular genetics of prostate cancer

“…Expression maintained even in androgenindependent tumors, although it is often amplified or mutated Culig et al 1998;Koivisto et al 1998) p53 Transcription/ apoptotic regulator Mutation rate in is low in primary cancer; frequently mutated in metastasis; p53 overexpression correlated with poor prognosis (Bookstein et al 1993;Effert et al 1993;Navone et al 1993;Thomas et al 1993;Aprikian et al 1994;Henke et al 1994;Voeller et al 1994;Bauer et al 1995;Eastham et al 1995;Heidenberg et al 1995;Shurbaji et al 1995;Moul et al 1996;Prendergast et al 1996;Matsushima et al 1997;Theodorescu et al 1997;Brewster et al 1999;Stackhouse et al 1999) …”

Hormone-refractory prostate cancer: a multi-step and multi-event process

“…27,30,31 Several other studies have demonstrated that p53 protein expression serves as an adverse prognostic indicator in prostate cancer. 29,32,33 The contribution of p53 protein inactivation to the resistance of prostatic epithelial cells to the effects of androgen deprivation is incompletely understood. In this regard, recent observations indicate that the level of p53 mRNA and protein increases in the regressing rat ventral prostate following castration.…”