The relative mRNA expression of p53 isoforms in breast cancer is associated with clinical features and outcome

Mutation of p53 is a common feature of cancer. Breast cancer is the most common malignancy that develops in women; however, somatic mutation of p53 is rare, suggesting that p53 becomes inactivated by other mechanisms. p53 is expressed as smaller isoforms, some of which inhibit wild-type p53. There are no studies that have examined the relative expression of all isoforms in this disease. We have analysed the relative messenger RNA expression of the p53 isoforms, 40, 133, and in a panel of 6 breast cancer cell lines, 148 breast cancers specimens and 31 matched normal adjacent tissues by semi-quantitative real-time reverse transcriptionPCR and analysed their relationship to clinical features and outcome. We have identified several important clinical associations, particularly with 40p53, which was expressed at levels that were similar to 50-fold higher than the least expressed isoform p53. 40p53 was significantly upregulated in tumour tissue when compared with the normal breast and was significantly associated with an aggressive breast cancer subtypeutriple negative. Additionally, p53 expression was significantly negatively associated with tumour size and positively associated with disease-free survival, where high levels of p53 were protective, particularly in patients with a mutation in p53, suggesting p53 may counteract the damage inflicted by mutant p53. In conclusion, the relative expression of p53 isoforms is related to clinical features of breast cancer and outcome. These results have implications for the stratification of breast cancer based on p53 function and may provide an alternate explanation for deregulated p53 signalling in breast cancer.