Prognostic Value of Cytosolic p53 Protein in Breast Cancer

Abstract

The prognostic value of cytosolic p53 protein was evaluated in 458 operable breast carcinomas by immunoblotting using the monoclonal antibody PAb 1801. Two hundred and five carcinomas (45%) showed positive p53 accumulation and 55% were p53 negative. When comparing p53 positivity and other clinicopathological parameters, significant differences were found with younger age (p = 0.017), premenopausal status (p = 0.003), increasing tumor size (p = 0.026), negative estrogen receptor (p = 0.003) and negative progesterone receptor (p = 0.047), but not with histologic grade, axillary lymph node status, stage or erbB-2 expression. With a median follow-up of 34 months (range 3–70), relapse has occurred in 73 patients. Disease-free survival curves showed that patients with p53-positive tumors had a significantly shorter disease-free survival than patients with p53-negative carcinomas (log-rank test, p = 0.027). A multivariate analysis of disease-free survival showed that p53, tumor size, histologic grade and progesterone receptor had significant independent prognostic value. The immunoblotting technique was controlled with p53 immunohistochemistry in 94 paired samples. We obtained a statistically significant correlation (p = 0.0004) between the two methods. Our results show that the immunoblotting technique offers an alternative approach in evaluating the p53 status of breast biopsy material using cytosolic extracts, and confirm that p53 accumulation is a significant independent indicator of a poor prognosis in operable breast carcinoma.

Association between polymorphisms of XRCC1, p53 and MDR1 genes, the expression of their protein products and prognostic significance in human breast cancer.

“…In agreement with Montero et al [23], disease-free survival curves showed that patients with p53-positive tumors had a significantly shorter disease-free survival compared to patients with p53-negative carcinomas. Tsutsui et al [24] confirmed the findings of Montero et al [23], and added that patients with p53-positive tumors had significantly worse overall survival compared to p53-negative patients.…”

The p53 positive Bcl‐2 negative phenotype is an independent marker of prognosis in breast cancer

“…Though Bcl‐2 expression has been found to be an independent predictor of prognosis,8, 23, 24, 25, 26, 44 in agreement with other work7, 11, 14, 17, 18, 27, 45 we found this not to be the case on multivariate analysis. Similarly, though some report mutant p53 as measured by IHC,7, 46, 12 immunoblotting46, 47 or denaturing gel electrophoresis48 to be an independent marker of reduced survival in breast cancer, in line with other work,8, 15 we found that p53 expression correlated with a reduction in survival in univariate but not multivariate analysis. Such observational discrepancies are likely to be due to the wide variation between methodologies and types of cases studied and we therefore intended to adhere to the REMARK guidelines to attempt a reproducible approach.…”

Flow cytometry and quantitative immunohistochemical study of cell cycle regulation proteins in invasive breast carcinoma

“…The same negative results that were obtained in the current study were shown in 4 of 10 studies concerning lymph node status, 81,90 -92 in 4 of 8 studies concerning patient age, 72,91,93,94 and in 3 of 11 studies concerning tumor size. 58,94,95 The same positive results that were obtained in the current study were found in 2 of 3 studies concerning mitotic activity, 95,96 58,72,77,81,84,87,91,92,95,[97][98][99] and in both studies concerning SPF. 72,95 In the current study, Ki-67 was not correlated with survival, p21 and cyclin A were correlated with survival of any type, and p53 was correlated with MFS.…”