Introduction
The tumour-suppressor protein p53 is a nuclear transcription factor that is autoregulatory in terms of expression, this being low in normal cells. Loss of p53 function is often associated with high accumulation of p53 and its retention in the cytoplasm. Abnormal accumulation of p53 in breast cancer tissue is predictive for poor prognosis [1,2]. Humoral studies [3,4] have shown that cancer patients may develop immunity to abnormally expressed p53, as revealed by p53 autoantibodies in the blood. Again, prognostic correlates have been noted, with presence of circulating p53 autoantibodies at diagnosis of breast cancer being associated with reduced overall survival [5,6] and with poor prognostic factors such as high histological grade and the absence of hormone receptors [5,7,8]. P53 dysfunction may be due to either mutational or epigenetic factors, each of which may lead to accumulation of cytoplasmic p53.
Little is known of the potential value of p53 autoantibody in follow-up of cancer. In lung cancer there is evidence that autoantibodies to p53 may provide a useful tool to monitor response to therapy [9,10], whereas serial measurements of autoantibodies to p53 in 40 patients with advanced ovarian cancer were not found to be clinically useful [11]. In breast cancer, some 30% of node-negative patients will relapse within 5 years, but there is no current means to predict those who are at risk. We have asked if the presence of autoantibodies to p53 have any association with disease progression by testing plasma samples taken from 1006 patients with breast cancer with a median follow-up period of 4 years.