1. ¹Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
2. ²Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
3. ³John L. McClellan Memorial Veterans Administration Hospital, Little Rock, Arkansas
4. ⁴College of Public Health, Sun-Yat Sen University, Guangzhou, People's Republic of China

Correspondence: Bruce R. Smoller, M.D., Director of Dermatopathology, Department of Pathology, University of Arkansas for Medical Sciences, 4301 West Markham, Slot 517, Little Rock, AR 72205; fax: 501-603-1479; e-mail: smollerbruce@exchange.uams.edu.

⁵MCC and LA contributed equally to the work presented in this article.

Accepted 20 June 2003.

Abstract

E-cadherin is a calcium-dependent, intercellular adhesion molecule that is specifically expressed in epithelial tissues and plays an important role in maintaining epithelial stability. E-cadherin is widely regarded as a prognostic marker in many types of human cancers. The inactivation of the E-cadherin gene is linked to increased potential for tumor invasiveness and distant metastasis. We previously demonstrated reduced expression of E-cadherin protein immunohistochemically in invasive squamous cell carcinomas of the skin as compared with adjacent normal skin. An epigenetic alteration in association with promoter hypermethylation is one important mechanism of gene silencing. In the present study, we analyze the E-cadherin gene promoter hypermethylation in preneoplastic and neoplastic skin lesions to determine whether epigenetic alteration of the E-cadherin gene also plays an important role in cutaneous squamous carcinogenesis. A total of 33 cases was examined for evidence of E-cadherin promoter hypermethylation, and these consist of nine cases of spongiotic dermatitis as nonneoplastic skin control, nine cases of actinic keratosis, eight cases of squamous cell carcinoma in situ, and seven cases of invasive squamous cell carcinoma. Promoter hypermethylation of the E-cadherin gene was detected in 6 of 7 cases (85%) of invasive squamous cell carcinoma, 4 of 8 cases (50%) of squamous cell carcinoma in situ, 4 of 9 cases (44%) of actinic keratosis, and 2 of 9 cases (22%) of nonneoplastic skin. We conclude that E-cadherin promoter hypermethylation occurs frequently and may represent an important mechanism of E-cadherin inactivation in cutaneous preneoplastic and neoplastic lesions. The frequencies of E-cadherin promoter hypermethylation appear to be correlated with more advanced stage of squamous carcinogenesis in skin.