J Breast Cancer.  2006 Jun;9(2):84-90. 10.4048/jbc.2006.9.2.84.

The Loss of p16(ink4)Expression is Strongly Associated with Hyperme thylation-Related Inactivation in Breast Carcinoma

• Gong G
• Kim MJ
• Shim YH
• Kang GH
• Ahn SH
• Ro JY

• KMID: 2286624
• DOI: http://doi.org/10.4048/jbc.2006.9.2.84

Abstract

PURPOSE
The loss of p16 protein has been frequently detected in breast carcinoma, but genetic alterations are infrequent. CpG islands of methylation within the p16 promotor have been identified as a mechanism that inactivates the p16 expression. The object of this study is to investigate the relationship between the loss of p16 protein and methylation as a molecular mechanism of the p16 gene inactivation in mammary tumorigenesis.
METHODS
: We performed an immunohistochemical assay of p16 protein in 70 cases of mammary carcinomas, and we tested for DNA methylation of p16 using methylation-specific PCR, and we then analyzed its correlation with the histopathologic variables.
RESULTS
: Among the 70 cases, the p16 expression was lost in 32 cases (45.7%), which was not significantly correlated with the pathologic variables. Twenty-three cases with and 27 cases without loss of p16 expression were tested for DNA methylation of p16. Twenty-one of the 23 interpretable cases with loss of p16 expression (91%) showed hypermethylation on p16, but there was no hypermethylation in any of the cases that were without the loss of the p16 expression.
CONCLUSION
These findings suggest that the loss of the p16 expression is one of the common abnormalities observed in breast carcinoma and that methylation on the 5'CpG island of the p16 promoter is a major process for p16 ink4 inactivation in breast carcinoma.

Keyword

breast neoplasm; loss of protein p16; methylation

MeSH Terms

Breast Neoplasms*
Breast*
Carcinogenesis
CpG Islands
DNA Methylation
Genes, p16
Methylation
Polymerase Chain Reaction

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