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Dysadherin: Expression and Clinical Significance in Thyroid Carcinoma

Pathology Division (H.S., Y.I., A.M., S.H.), National Cancer Center Research Institute, Tokyo 104-0045, Japan; Department of Medicine (Y.A., H.S.), Tokai University School of Medicine, Kanagawa 259-1193, Japan; and Ito Hospital (K.I.), Tokyo 150-8308, Japan

Address all correspondence and requests for reprints to: Setsuo Hirohashi, M.D., Director, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. E-mail: shirohas{at}ncc.go.jp.

Dysadherin is a cancer-associated cell membrane glycoprotein. Its cDNA encodes 178 amino acids, including a putative signal sequence, a potential O-glycosylated extracellular domain, a single transmembrane domain, and a short cytoplasmic tail. Dysadherin is believed to down-regulate the expression of E-cadherin, the prime mediator of cell-cell adhesion in epithelial cells, by a posttranscriptional mechanism and promote the metastasis of carcinoma cells. To evaluate the association between dysadherin expression and E-cadherin expression in thyroid carcinoma, immunostaining for dysadherin and E-cadherin was performed in 51 papillary, 10 follicular, and 31 undifferentiated carcinomas. Immunoreactivity for dysadherin, localized at cell-cell boundaries, was detected in 39 of the 51 papillary carcinomas and all 31 undifferentiated carcinomas but not in the follicular carcinomas or normal thyroid tissue controls. Dysadherin expression was significantly higher in undifferentiated carcinoma than in papillary carcinoma and follicular carcinoma and showed significant negative correlation with E-cadherin expression. The degree of dysadherin expression was significantly associated with the prognosis, occurrence of secondary undifferentiated carcinomas, size of the primary tumor, and metastasis to the regional lymph nodes and lungs. In conclusion, a process involving increased dysadherin expression may lead to an adverse clinical outcome.

This work was supported by a Grant-in-Aid for the Second Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labor, and Welfare of Japan and 2002 Tokai University School of Medicine Research Aid.

Abbreviations: FC, Follicular carcinoma; PC, papillary carcinoma; TNM, tumor-node-metastasis; UC, undifferentiated carcinoma.

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