PMID- 10987229
OWN - NLM
STAT- MEDLINE
DCOM- 20000928
LR  - 20220409
IS  - 0284-186X (Print)
IS  - 0284-186X (Linking)
VI  - 39
IP  - 3
DP  - 2000
TI  - TP53 mutation is an independent prognostic marker for poor outcome in both 
      node-negative and node-positive breast cancer.
PG  - 327-33
AB  - TP53 gene-mutation and protein expression of p53 are described as being of 
      prognostic importance for the outcome of breast cancer. The present study was 
      therefore carried out to evaluate whether TP53 mutation would be a feasible 
      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 guidelines of the Danish 
      Breast Cancer Cooperative Group for the DBCG 89 protocols. The results were 
      correlated with clinico-pathological parameters and the prognosis evaluated by 
      uni- and multivariate analysis using local control, freedom from distant 
      metastasis, disease-free survival, and overall survival as endpoints. The study 
      included 294 patients. TP53 mutations were found in 23% of cases. Mutations were 
      significantly more frequent in tumours from patients who were node-positive and 
      with tumours characterized as being ductal, large of size, with a high degree of 
      anaplasia, and oestrogen receptor negative. Using univariate analysis, it was 
      found that distant metastasis, disease-free, and overall survival were correlated 
      to tumour size, nodal status, degree of anaplasia, oestrogen receptor status, and 
      TP53 mutation. In addition, overall survival was also correlated to age and 
      menopausal status. When analysed according to nodal status, TP53 mutation was 
      found to have a significantly poor survival probability in each of the subgroups. 
      A Cox proportional hazard analysis, including all 294 patients, demonstrated that 
      positive nodal status and TP53 mutation were the only parameters that had an 
      independent poor influence on the risk of developing distant metastasis and 
      reduced recurrence-free survival. The same factors together with postmenopausal 
      status were found to be significantly associated with increased risk of death. 
      TP53 mutation is a strong marker for the prediction of overall and disease-free 
      survival in breast cancer, irrespective of nodal status. A better understanding 
      of the role of the p53 pathway, including analysis of different types of TP53 
      mutations, is required in order further to investigate the prognostic potential 
      of this marker.
FAU - Overgaard, J
AU  - Overgaard J
AD  - Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus 
      University Hospital. Jens@oncology.dk
FAU - Yilmaz, M
AU  - Yilmaz M
FAU - Guldberg, P
AU  - Guldberg P
FAU - Hansen, L L
AU  - Hansen LL
FAU - Alsner, J
AU  - Alsner J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Sweden
TA  - Acta Oncol
JT  - Acta oncologica (Stockholm, Sweden)
JID - 8709065
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (DNA, Neoplasm)
SB  - IM
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*analysis
MH  - Breast Neoplasms/*genetics/pathology
MH  - DNA Mutational Analysis
MH  - DNA, Neoplasm/*genetics
MH  - Disease-Free Survival
MH  - Female
MH  - Genes, p53/*genetics
MH  - Humans
MH  - Lymph Nodes/*pathology
MH  - Lymphatic Metastasis
MH  - Menopause
MH  - Middle Aged
MH  - Polymerase Chain Reaction
MH  - Prognosis
MH  - Retrospective Studies
EDAT- 2000/09/15 11:00
MHDA- 2000/09/30 11:01
CRDT- 2000/09/15 11:00
PHST- 2000/09/15 11:00 [pubmed]
PHST- 2000/09/30 11:01 [medline]
PHST- 2000/09/15 11:00 [entrez]
AID - 10.1080/028418600750013096 [doi]
PST - ppublish
SO  - Acta Oncol. 2000;39(3):327-33. doi: 10.1080/028418600750013096.