p53 autoantibodies in patients with malignant mesothelioma: stability through disease progression

Malignant mesothelioma (MM) generally occurs as a pleural tumour, related t o the inhalation of asbestos fibres. It is highly aggressive and largely un responsive to treatment. The incidence of MM is particularly high in Wester n Australia because of the extensive blue asbestos mining operations that o ccurred in the north of the state until 1966. MM is unusual in that mutatio ns in the tumour suppressor gene p53 are rarely observed, whilst over-expre ssion of p53 protein is common. As the level of antibodies directed against p53 is thought to be of prognostic value in some cancers and as MM is know n to be immunogenic, we studied a cohort of Western Australian patients to determine the prevalence of anti-p53 antibodies and their value as diagnost ic markers or prognostic indicators. 6/88 (7%) of patients had high titres (>2 SD above the mean of controls) of anti-p53 antibodies. There was no cor relation between antibody titre and survival. Although 3/38 (8%) of sera ob tained from patients exposed to asbestos but prior to a diagnosis of MM con tained antibodies, the same proportion of sera obtained from patients expos ed to asbestos but who remained disease free also contained antibodies (2/4 0; 8%). Sera collected sequentially demonstrated a profound temporal stabil ity in the titre of anti-p53 antibodies in patients with MM throughout the course of their illness. These results show that anti-p53 antibodies are ob served only at a low frequency in the sera of MM patients and where they do occur, their elicitation is an early event that may be unrelated to antige n load. The occurrence of anti-p53 antibodies does not serve as either a us eful prognostic or diagnostic indicator in MM. (C) 2001 Cancer Research Cam paign http://www.bjcancer.com.