Mutant p53 protein overexpression is associated with poor outcome in patients with well or moderately differentiated ovarian carcinoma

Abstract

Background. It has been shown that the p53 gene is mutated in 30‐80% of ovarian carcinomas and that the genetic alterations most often manifest as an accumulation of mutant p53 protein in tumor tissue. The prognostic significance of these findings for patients with ovarian cancer, however, must be established clearly. Methods. Mutant p53 protein in 90 consecutive epithelial ovarian carcinomas was quantitatively analyzed using a time‐resolved immunofluorometric procedure. In contrast to immunohistochemical techniques, this method uses two anti‐p53 antibodies. The Cox model was used to evaluate the strength of the associations between the prognostic markers and disease relapse or death at univariate and multivariate levels. Kaplan‐Meier survival curves were calculated for patients who were p53‐positive or negative and for subgroups with a different clinical stage, histologic grade, or residual postsurgical tumor. Results. The positivity rates for p53 included 1/21 (5%) with Stage I disease, 1/6 (17%) with Stage II, 29/51 (57%) with Stage III, and 8/12 (67%) with Stage IV (total = 39/90, 43%). Patients with p53‐negative tumors had a significantly longer disease free survival than did patients with p53‐positive tumors (P = 0.03); these results were similar for overall survival (P = 0.06). Multivariate analysis revealed that the presence of postsurgical residual tumor was the only predictor significantly associated with poor patient outcome. However, when patients were divided into groups based on histologic grade, patients with well (G1) and moderately (G2) differentiated tumors had a significantly higher risk of cancer relapse and death if mutant p53 protein was present in their tumors compared with patients who were negative for mutant p53 protein (<0.01). Conclusions. The immunofluorometric measurement of mutant p53 protein accumulation in epithelial ovarian carcinomas of a low histologic grade was associated significantly with an increased risk for cancer relapse and death. A similar trend also was suggested for early stage disease and in the absence of residual tumor after surgery. These increased risks, however, were not found for patients with high grade or advanced stage cancer or for those with residual tumor. To the authors' knowledge, this is the first report suggesting that p53 tumor protein accumulation is a marker of poor prognosis in a subset of patients with ovarian cancer. Cancer 1995;75:1327‐38.

p21/WAF1 expression as related to p53, cell proliferation and prognosis in epithelial ovarian cancer

“…Similar data have been observed in other studies, where p53-positivity has significantly predicted a poor survival (Henriksen et al, 1994;Klemi et al, 1995;van der Zee et al, 1995;Herod et al, 1996). However, contradictory results have been reported as well (Marks et al, 1991;Kohler et al, 1993a;Levesque et al, 1995). The observed prognostic significance of Ki-67 in the present study is consonant with the data of Garzetti et al (1995).…”

A review of p53 expression and mutation in human benign, low malignant potential, and invasive epithelial ovarian tumors

“…112,113 p53 expression was detected by immunohistochemical staining in all but two studies that used immunofluorometric assays. 83,84 The monoclonal antibodies D0-7 and PAb-1801 (which detect both wildtype and mutant p53 protein) were the most common primary antibodies, and were used in 36 studies 14-16,19, 21,23,25,28,29,32,34,37,38,46,48,52,53,55,72,78,80 -82,85,87,89,92,95 15,17,49,87 Four studies used a combination of paraffin-embedded and frozen tissue, 18,53,82,92 one study used imprints from biopsies, 25 and one study did not report on the tissue type used.…”

Biological Malignancy Grading in Early-Stage Ovarian Carcinoma

“…Only a few studies have been successful in showing a relationship between p53 expression and clinical outcome (21,22). Levesque et al (22) have shown that mutant p53 protein accumulation in early stage tumours with low histological grade was associated with an increased risk of cancer relapse.…”