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Clinicopathologic significance of dysadherin expression in cutaneous malignant melanoma: immunohistochemical analysis of 115 patients.

Nishizawa A, Nakanishi Y, Yoshimura K, Sasajima Y, Yamazaki N, Yamamoto A, Hanada K, Kanai Y, Hirohashi S

Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.

BACKGROUND: The E-cadherin-mediated cell adhesion system is frequently inactivated by multiple mechanisms and is involved in tumor progression in many types of cancer. Recently, the authors reported a novel cell membrane glycoprotein, dysadherin, which has an anti-cell-cell adhesion function and down-regulates E-cadherin. METHODS: Expression of both dysadherin and E-cadherin was investigated immunohistochemically in 115 patients with cutaneous malignant melanoma to determine the correlation between the 2 molecules and their associations with both patient survival and the clinicopathologic features of the tumors. RESULTS: Dysadherin and E-cadherin were expressed at the cell membranes of melanoma cells. Fifty-two percent of the tumors showed dysadherin immunopositivity, and 91% of the tumors showed reduced E-cadherin immunopositivity. There was no significant inverse correlation between dysadherin expression and E-cadherin expression. Increased dysadherin expression was significantly correlated with nodular subtype (P = 0.042), Clark level (P < 0.001), tumor thickness (P < 0.001), ulceration (P = 0.008), lymph node metastasis (P < 0.001), high TNM classification (P < 0.001), and poor patient survival (P < 0.001). Multivariate analysis of patient survival revealed that increased dysadherin expression was a significant predictor of poor survival (P < 0.001). CONCLUSIONS: Thus, increased expression of dysadherin was a significant indicator of poor prognosis in patients with cutaneous malignant melanoma.

Published 13 April 2005 in Cancer, 103(8): 1693-700.
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