It was thus concluded that the detection of p53 gene mutation by PCR-SSCP analysis of aspirated biopsy specimens from suspected breast cancers is a helpful method for achieving a more accurate diagnosis.
Furthermore, the oh8dG levels in breast cancers were not associated with p53 and erbB-2 immunoreactions, with expression of estrogen and progesterone receptors, and with clinical stage and histological grade.
Node-negative breast cancer patients with p53 mutations had significantly improved relapse-free survival (P = .0007), breast cancer-corrected survival (P = .01), and overall survival (P = .02) rates when treated with locoregional radiotherapy.
Overexpression of p53 protein was closely associated with increasing tumour size and ER-negative status among the various factors investigated, suggesting that p53 overexpression may reflect the lack of differentiation in breast cancer.
The present study assessed the p53 gene status, ability to arrest in G1 of the cell cycle, the functionality of the p53 transduction pathway, and apoptosis following treatment with radiation in a series of drug-resistant human breast cancer cells to determine whether p53 alterations occur during the development of drug resistance.
We have tested this hypothesis using retrovirally transduced wild-type (wt) p53 in breast cancer cell lines containing homozygously endogenous mutant (mt) p53.
These results indicate that these biochemically defined domains also have biological relevance in terms of breast cancer disease course, and suggest that some mutations in TP53, more than others, can contribute to the development of clinically more aggressive and perhaps treatment resistant breast tumours.
The results lend further support to the view that inherited mutations in p53 alleles are not a significant contributor to breast cancer predisposition and it is not, therefore, clinically worthwhile to screen predisposed or potentially predisposed families for germline mutations in the p53 gene.
Other high-risk cancer genes that confer increased risks of breast or ovarian cancer in addition to other cancers include the hereditary non-polyposis colorectal cancer genes and the TP53 gene, which causes breast cancer as part of the Li-Fraumeni syndrome.
In summary, a new sensitive and quantitative LIA suitable for routine analysis of p53 protein in steroid receptor cytosol preparations from breast tumours has been developed to confirm the prognostic importance of p53 protein accumulation in human breast cancer.
The results suggest that the allelic deletion of p53 may also contribute to the development and progression of breast cancer by reducing the amount of normal p53 protein.
Alterations in the expression of ras p21, p53 and c-erbB-2 have all been linked to tumours with rapid cellular proliferation, but the evidence that they are of prognostic importance in patients with breast cancer is conflicting.
Complete sequencing of the p53 gene provides prognostic information in breast cancer patients, particularly in relation to adjuvant systemic therapy and radiotherapy.
Recently, linkage analyses of large families with a predisposition to breast cancer have been performed in order to map breast cancer susceptibility genes (TP53, BRCA1, BRCA2).