The Loss of P16ink4 Expression is Strongly Associated with Hypermethylation-Related Inactivation in Breast Carcinoma

Gyungyub Gong; Mi-Jung Kim; Yhong-Hee Shim; Gyeong Hoon Kang; Sei Hyun Ahn; Jae Y. Ro

doi:10.4048/jbc.2006.9.2.84

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Gong, Kim, Shim, Kang, Ahn, and Ro: The Loss of P16ink4 Expression is Strongly Associated with Hypermethylation-Related Inactivation in Breast Carcinoma

Original Article

Journal of Breast Cancer

Journal of Breast Cancer 2006; 9(2): 84-90.

Published online: 30 June 2006

DOI: https://doi.org/10.4048/jbc.2006.9.2.84

The Loss of P16^ink4 Expression is Strongly Associated with Hypermethylation-Related Inactivation in Breast Carcinoma

Gyungyub Gong, Mi-Jung Kim, Yhong-Hee Shim¹, Gyeong Hoon Kang², Sei Hyun Ahn³, Jae Y. Ro⁴

Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

¹Department of Biological Science, Konkuk University, Seoul, Korea.

²Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.

³Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

⁴Department of Pathology, Methodist Hospital, Houston, USA.

Correspondence: Gyungyub Gong. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736, Korea. Tel 82-2-3010-4554, Fax 82-2-472-7898, gygong@amc.seoul.kr

Received 10 February 2006 Accepted 12 April 2006

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.

Keywords: breast neoplasm, loss of protein p16, methylation

Notes

This study was supported by a research grant (2001-169) from the Asan Institute for Life Sciences and Korea Breast Cancer Foundation (2004)

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