Korean J Pathol.  2005 Oct;39(5):313-319.

Mutational and Loss of Heterozygosity Analysis of the p53 and PTEN Tumor Suppressor Genes in Breast Carcinoma

• Suh KS
• Lee YH
• Na SY
• Park MI
• Kim HS
• Lee SK

Abstract

BACKGROUND: Although the genetic determinants of most sporadic breast cancers remain unknown, the understanding of the molecular and genetic events that contribute to breast carcinogenesis has been significantly advanced. We investigated the clinicopathologic significance of allelic imbalance or mutation of both p53 and PTEN tumor suppressor genes in sporadic breast carcinomas.
METHODS
Genomic DNA from 62 breast carcinoma cases was extracted from paraffin blocks, and PCR was performed to determine loss of heterozygosity (LOH) for DNA markers around the p53 and PTEN genes and to amplify exons 5, 6, 7, and 8 of p53 and all 9 coding axons of PTEN.
RESULTS
Somatic p53 mutations were detected in 6 (9.7%) of the 62 cases. LOH for DNA markers surrounding p53 was observed in 18 (29.0%) of the 62 cases. LOH for DNA markers surrounding PTEN was detected in 29 (46.8%) of the 62 cases. Only one case (1.6%) showed somatic PTEN mutations. Tumors with LOH on 17p or p53 mutation were large in size and negative for ER, had a high Ki-67 index, and exhibited p53 immunoreactivity (p<0.05). Tumors with LOH on 10q23 were associated with c-erbB-2 positivity (p=0.018).
CONCLUSIONS
Our results indicate that LOH at 17p and/or p53 mutation is significantly associated with the aggressive pathologic parameters of breast cancer.

Keyword

Carcinoma, Breast; Genes p53; PTEN protein; Mutation; Loss of heterozygosity

MeSH Terms

Allelic Imbalance
Axons
Breast Neoplasms*
Breast*
Carcinogenesis
Clinical Coding
DNA
Exons
Genes, Tumor Suppressor*
Genetic Markers
Loss of Heterozygosity*
Paraffin
Polymerase Chain Reaction
PTEN Phosphohydrolase
DNA
Genetic Markers
PTEN Phosphohydrolase
Paraffin