Introduction: 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.
Methods: Expression of p53 beta and p53 gamma isoforms, the isoforms identified in normal breast tissue, was detected by reverse transcription polymerase chain reaction from a cohort of 127 primary breast tumours. Expression of p53 beta and p53 gamma isoforms was analysed in relation to clinical markers and clinical outcomes (5 years) by binary logistic regression, Cox proportional hazards regression and Kaplan-Meier survival analyses.
Results: p53 beta and p53 gamma were not randomly expressed in breast cancer. p53 beta was associated with tumour oestrogen receptor (ER) expression, and p53 gamma was associated with mutation of the p53 gene. The patient group with the mutant p53 breast tumour-expressing p53 gamma isoform had low cancer recurrence and an overall survival as good as that of patients with wild-type p53 breast cancer. Conversely, patients expressing only mutant p53, without p53 gamma isoform expression, had a particularly poor prognosis.
Conclusions: The determination of p53 gamma expression may allow the identification, independently of the ER status, of two subpopulations of mutant p53 breast cancer patients, one expressing p53 gamma with a prognosis as good as the wild-type p53 breast cancer patients and a second one not expressing p53 gamma with a particularly poor prognosis. The p53 gamma isoform may provide an explanation of the hitherto inconsistent relationship between p53 mutation, treatment response and outcome in breast cancer.
- TP53 GENE-MUTATIONS
- NEOADJUVANT TREATMENT
- CELL CARCINOMA