Prognostic significance of TP53 alterations in breast carcinoma

Constant denaturant gel electrophoresis (CDGE) was used to screen 179 breast carcinomas for mutations in the conserved regions of the TP53 gene (exons 5 through 8). Mutations were found in 35 of 163 primary tumours (21%) and in 5 of 16 metastases (31%) and resided predominantly in exon 7. The majori...

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Bibliographic Details
Published in:British journal of cancer 1993-09, Vol.68 (3), p.540-548
Main Authors: ANDERSEN, T. I, HOLM, R, NESLAND, J. M, HEIMDAL, K. R, OTTESTAD, L, BØRRESEN, A.-L
Format: Article
Language:English
Subjects:
Adult
Aged
Biological and medical sciences
Breast Neoplasms - genetics
Female
Genes, p53
Gynecology. Andrology. Obstetrics
Humans
Immunohistochemistry
Mammary gland diseases
Medical sciences
Middle Aged
Multivariate Analysis
Mutation
Oncogene Proteins, Viral - genetics
Prognosis
Receptor, ErbB-2
Receptors, Estrogen - analysis
Receptors, Progesterone - analysis
Time Factors
Tumor Suppressor Protein p53 - metabolism
Tumors
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Summary:Constant denaturant gel electrophoresis (CDGE) was used to screen 179 breast carcinomas for mutations in the conserved regions of the TP53 gene (exons 5 through 8). Mutations were found in 35 of 163 primary tumours (21%) and in 5 of 16 metastases (31%) and resided predominantly in exon 7. The majority of the mutations were G:C-->A:T transitions. Immunohistochemistry demonstrated nuclear accumulation of p53 protein in 35 of 162 primary tumours (22%) and in four of 15 metastases (27%). TP53 mutation was strongly associated with nuclear accumulation of p53 protein. In total 42 of 163 primary tumours (26%) and 5 of 16 metastases (31%) were demonstrated to contain TP53 alterations (mutation and/or nuclear protein accumulation). TP53 alteration in primary tumour was significantly associated with the following parameters: positive node status, T status > 1, negative oestrogen receptor status, negative progesterone receptor status, presence of ERBB2 gene amplification, and invasive ductal histology. Furthermore, there were statistically significant associations, independent of other prognostic factors, between TP53 alterations in primary tumour and disease-free and overall survival.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.1993.383