p53 mutant breast cancer patients expressing p53γ have as good a prognosis as wild-type p53 breast cancer patients.
BACKGROUND
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 p53β and p53γ 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 p53β and p53γ 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
p53β and p53γ were not randomly expressed in breast cancer. p53β was associated with tumour oestrogen receptor (ER) expression, and p53γ was associated with mutation of the p53 gene. The patient group with the mutant p53 breast tumour-expressing p53γ 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 p53γ isoform expression, had a particularly poor prognosis.


CONCLUSIONS
The determination of p53γ expression may allow the identification, independently of the ER status, of two subpopulations of mutant p53 breast cancer patients, one expressing p53γ with a prognosis as good as the wild-type p53 breast cancer patients and a second one not expressing p53γ with a particularly poor prognosis. The p53γ isoform may provide an explanation of the hitherto inconsistent relationship between p53 mutation, treatment response and outcome in breast cancer.
Centre for Oncology and Molecular Medicine, Inserm-European Associated Laboratory, University of Dundee, Dundee, DD1 9SY, UK. j.bourdon@dundee.ac.uk
Jean-Christophe
JC
Bourdon
Marie P
MP
Khoury
Alexandra
A
Diot
Lee
L
Baker
Kenneth
K
Fernandes
Mustapha
M
Aoubala
Philip
P
Quinlan
Colin A
CA
Purdie
Lee B
LB
Jordan
Anne-Catherine
AC
Prats
David P
DP
Lane
Alastair M
AM
Thompson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics; D012008:Recurrence; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53
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