Overexpression of cyclin A overrides the effect of p53 alterations in breast cancer patients with long follow-up time

The tumour suppressor gene p53 and its protein controls critical cellular functions in cell cycle regulation as well as in apoptosis. Recently, in an in vitro study on breast cancer cell line MCF-7, the apoptotic function of p53 has been shown to be altered by overexpression of cyclin A. In this study we have demonstrated a similar association in a consecutive series of 166 breast cancer patients operated for invasive breast carcinomas. We detected mutations (exon 5-8) in the tumour tissue from 28 (16.0%) of the patients, and positive immunoreactivity of p53 protein was detected in tumour tissue samples from 32 (18.8%) patients. A statistically significant correlation between TP53 gene mutations and positive immunohistochemistry of p53 protein was observed (p=0.0038). Mutations of the TP53 gene, as well as positive immunoreactivity to p53, were associated with poor prognosis (mutations p=0.053, HR=1.8, 95% CI 0.99-3.4; positive immunoreactivity p=0.029, HR 1.33, 95% CI 1.0-1.7; mutation and/or positive immunoreactivity p=0.015, HR 2.1, 95% CI 1.2-3.7) when cyclin A was not included in the survival analysis. However, when cyclin A overexpression was included, alteration of the p53 protein (mutations and/or positive immunoreactivity) lost its statistical power (p=0.088). In a stratified survival analysis the OR fell from 3.0 (95% CI 1.2-8.3, p=0.03) in the low-expression cyclin A stratum to 1.3 (95% CI 0.42-4.1, p=0.77) in the overexpression cyclin A stratum.