A cyclin-dependent kinase (CDK) 4 inhibitor (p16INK4) gene located at 9p21 has been shown to be inactivated in a variety of tumors by homozygous deletions, point mutations, or hypermethylation of its promoter region. The etiologic role of the cdk inhibitor p16^INK4a tumor suppressor protein in breast cancer remains unclear. This study attempts to assess the methylation pattern of p16^INK4a gene and its correlation with the expression of p16^INK4a and to determine, by comparing the correlation between other standard immunohistochemical parameters (Cerb B2, estrogen receptor, progesteron receptor, p53, and Ki-67) and clinicopathological features, the significance of p16^INK4a methylation and p16^INK4a immunohistochemical expression in breast carcinoma. Immunohistochemical p16^INK4a expression was found in 21 (42%) of 50 cases. There was a correlation between loss of p16^INK4a expression and advanced stage (p=.016). p16^INK4a promoter methylation was found in 72%. Twenty-three (79.3%) of 29 tumors with loss of expression of p16^INK4a in immunohistochemistry showed DNA methylation of the p16^INK4a gene. Loss of p16^INK4a expression was related with high stage breast tumors and p16^INK4a promoter hypermethylation was the main mechanism of loss of p16^INK4a expression. (Cancer Prev Res 13, 85-90, 2008)

Keywords: p16^INK4a, Methylation, Immunohistochemistry, Breast cancer