J. Overgaard et al., TP53 mutation is an independent prognostic marker for poor outcome in bothnode-negative and node-positive breast cancer, ACTA ONCOL, 39(3), 2000, pp. 327-333
TP53 gene-mutation and protein expression of p53 are described as bring of
prognostic importance for the outcome of breast cancer. The present study w
as therefore carried out to evaluate whether TP53 mutation would be a feasi
ble prognostic marker in the routine diagnostic evaluation of breast cancer
, and, in particular, to analyse the relationship between TP53 mutation and
nodal status. Tumour material was obtained from women with sporadic early
breast cancer. Gene mutations in exon 2-11 were identified using denaturing
gradient gel electrophoresis (DGGE) as the initial scanning procedure and
characterized by sequencing. All patients were treated according to the gui
delines of the Danish Breast Cancer Cooperative Group for the DBCG 89 proto
cols. The results were correlated with clinico-pathological parameters and
the prognosis evaluated by uni- and multivariate analysis using local contr
ol, freedom from distant metastasis, disease-free survival, and overall sur
vival as endpoints. The study included 294 patients. TP53 mutations were fo
und in 23% of cases. Mutations were significantly more frequent in tumours
from patients who were node-positive and with tumours characterized as bein
g ductal, large of size, with a high degree of anaplasia, and oestrogen rec
eptor negative. Using univariate analysis, it was found that distant metast
asis, disease-free, and overall survival were correlated to tumour size, no
dal status, degree of anaplasia, oestrogen receptor status, and TP53 mutati
on. In addition, overall survival was also correlated to age and menopausal
status. When analysed according to nodal status, TP53 mutation was found t
o have a significantly poor survival probability in each of the subgroups.
A Cox proportional hazard analysis: including all 294 patients, demonstrate
d that positive nodal status and TP53 mutation were the only parameters tha
t had an independent poor influence on the risk of developing distant metas
tasis and reduced recurrence-free survival. The same factors together with
postmenopausal status were found to be significantly associated with increa
sed risk of death. TP53 mutation is a strong marker for the prediction of o
verall and disease-free survival in breast cancer, irrespective of nodal st
atus. A batter understanding of the role of the p53 pathway, including anal
ysis of different types of TP53 mutations, is required in order further to
investigate the prognostic potential of this marker.