Expression of catenins and p120cas in melanocytic nevi and cutaneous melanoma: deficient alpha-catenin expression is associated with melanoma progression.

E-cadherin mediated intercellular adhesion is regulated by a family of cytoplasmic proteins that include alpha-, beta- and gamma-catenin and p120cas. Changes in expression of E-cadherin are believed to be an early event in melanoma development. Recent studies have also drawn attention to the over-expression of beta-catenin and its possible indirect role as an oncogene in melanoma. In view of these studies, we have examined the expression of cytoplasmic proteins immunohistochemically in 13 melanocytic nevi, 34 primary cutaneous melanomas and 20 metastatic melanomas. alpha-, gamma-catenin and p120cas were heterogeneously expressed in melanocytic nevi and melanomas and were frequently absent, whereas beta-catenin expression was observed in all lesions. The pattern of expression of alpha-, beta- and gamma-catenin and p120cas was characterised by cytoplasmic and membranous immunoreactivity of varying intensity. No significant difference was found in expression of these proteins between melanocytic nevi and primary melanoma. In contrast, there was an inverse correlation between alpha-catenin expression and tumor thickness and alpha-catenin was more frequently expressed in radial compared to vertical growth phase in primary melanoma. Loss of alpha-catenin expression was observed in ten of 20 metastases compared to six of 34 primaries and the expression was more marked in primaries than in metastases. These results indicated that alterations in alpha-, beta- and gamma-catenin and p120cas expression were common in melanocytic nevi and melanomas, and that loss of alpha-catenin expression was associated with melanoma invasiveness and metastasis.