Normal function of the p53 network is lost in most cancers, often through p53 mutation. The clinical impact of p53 mutations in breast cancer remains uncertain, especially where p53 isoforms may modify the effects of these p53 mutations.

Expression of p53beta and p53gamma isoforms, the isoforms identified in normal breast tissue, was detected by reverse-transcription PCR from a cohort of 127 primary breast tumours. Expression of p53beta and p53gamma isoforms was analysed in relation to clinical markers and clinical outcome (5 years) by Binary Logistic Regression, Cox's regression and Kaplan Meier analyses.

p53beta and p53gamma were not randomly expressed in breast cancer. p53beta was associated with tumour estrogen receptor (ER) expression and p53gamma was associated with mutation of the p53 gene. The patient group with mutant p53 breast tumour expressing p53gamma isoform had low cancer recurrence and an overall survival as good as patients bearing wild-type p53 breast cancer. Conversely, patients expressing only mutant p53, without p53gamma isoform expression, had a particularly poor prognosis.

The determination of p53gamma expression may allow the identification, independently of the ER status, of two subpopulations of mutant p53 breast cancer patients, one expressing p53gamma with a prognosis as good as the wild-type p53 breast cancer patients and a second one not expressing p53gamma with a particularly poor prognosis. The p53gamma isoform may provide an explanation of the hitherto inconsistent relationship between p53 mutation, treatment response and outcome in breast cancer.

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