p53 gene mutations and expression of p53 and mdm2 proteins in invasive breast carcinoma: A comparative analysis with clinico-pathological factors
Open accessAbstract
The aim of the study was to analyze p53 gene mutations and the expression of p53 and mdm2 proteins in 31 randomly selected invasive breast carcinomas. The results were then correlated with tumor grade, stage, estrogen receptor status, nodal status, and DNA ploidy. The expression of the proteins p53 and mdm2 was determined immunohistochemically using formalin-fixed, paraffin-embedded material. Screening for p53 mutation involved analysis of the highly conserved regions of the p53 gene (exons 5-9) by the polymerase chain reaction/ single-strand conformation polymorphism (PCR-SSCP) technique. PCR products with band shifts were directly sequenced. Immunohistochemical staining of p53 was positive in 9 cases (29.0%), only 2 of which showed a p53 gene mutation. These were identified as a C-->G transversion at the second position of codon 278 in exon 8 and an A-->G transition at the second position of codon 205 in exon 6. A third case with a mutation was observed (C-->T transition, position 1 of codon 250 in exon 7) that did not show p53 immunohistochemically. Of the 9 p53-positive tumors, 2 were moderately differentiated (grade II). The remaining tumors were poorly differentiated (7/9). By contrast, p53-negative carcinomas were well differentiated (grade I) in most cases (P = 0.02). DNA cytometry in 8 of the 9 p53-positive carcinomas revealed an aneuploid stem line. The majority of the p53-negative tumors were diploid (P = 0.01). Mdm2 oncoprotein was detected in 10 tumors (32.2%), 4 of which were p53-positive, including the 3 with mutations. The grading of the mdm2-positive tumors was moderate or poor, G1 carcinomas were always noted to be mdm2-negative (P = 0.04). Overexpression of p53 protein is a complex mechanism and does not merely indicate the detection of mutations in the p53 gene. This study has shown that p53 expression correlates with tumor grade and DNA ploidy. Mdm2 expression was also associated with the tumor grade. Immunohistological demonstration of the p53 protein alone is insufficient as a basis for comment on the functional state of the p53 gene and gene product. The interrelation between recognition of the p53 protein and gene mutation needs more careful assessment to define their roles in the control of neoplasia.
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Some tumor cells contain both inactivated TP53 and overexpressed MDM2 and/or MDM4.
“some tumor cells contain both inactivated TP53 and overexpressed MDM2 and/or MDM4”
From The Mdm network and its regulation of p53 activities: a rheostat of cancer risk (2014) · cites this paper as Gunther, et al., 1997
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- Authors
- Günther, T., Schneider-Stock, R., Ryš, J., Niezabitowski, A., & Roessner, A.
- Affiliations
- Otto-von-Guericke-Universität Magdeburg (DE)
- ORCID
- Roessner, A.
- Venue
- Journal of Cancer Research and Clinical Oncology
- Published
- 1997-07
- Volume
- 123
- Issue
- 7
- Pages
- 388-394
- ISSN
- 0084-5353 (ISSN-L)
- 0171-5216
- 1432-1335
- PMC
- PMC12200188
- OpenAlex
- W2315537362
- Cited by
- 28
- References
- 50
- Citations by year
- 2026: 1 · 2021: 2 · 2016: 1 · 2014: 1 · 2013: 1
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Cancer Research and Clinical Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- p53 expression, MDM2, invasive breast cancer, tumor grade, DNA ploidy, aneuploidy, estrogen receptor status, tumor stage, lymph node status, p53 overexpression
- MeSH terms
- Adult, Aged, Breast Neoplasms, Carcinoma, DNA, Neoplasm, Female, Humans, Middle Aged, Mutation, Nuclear Proteins, Ploidies, Proto-Oncogene Proteins, Receptors, Estrogen, Gene Expression Regulation, Neoplastic, Genes, p53, Tumor Suppressor Protein p53, Point Mutation, Polymorphism, Single-Stranded Conformational, Proto-Oncogene Proteins c-mdm2
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