Alterations in cadherin and catenin expression during the biological progression of melanocytic tumours

Aims-Compelling evidence from cell culture studies implicates cadherins in the neoplastic progression of melanocytic tumours but few reports describe the expression of cadherins and the related transmembrane proteins, catenin s, in a full range of benign and malignant excised melanocytic tumours. Methods-Using immunohistochemistry and western blotting after tissue fracti onation, the pattern of expression of cadherins/ catenins was studied in a range of surgically excised melanocytic tumours, from dysplastic naevi to s tage III cutaneous metastatic malignant melanoma. Results-Appropriate membranous expression of E-cadherins and P-cadherins is seen in dysplastic naevocytes with an epithelioid phenotype and is largely maintained with malignant transformation to radial growth phase melanoma a nd primary vertical growth phase malignant melanoma. Loss of membranous E-c adherin is seen in a small number of vertical growth phase melanomas only w hen metastasis has occurred. However, there is a concomitant dramatic loss of membranous P-cadherin expression in all melanomas at the same stage. A m inority of metastatic melanomas show de novo membranous N-cadherin expressi on in comparison with dysplastic naevi and primary melanoma. Membranous exp ression of the desmosomal cadherin, desmoglein, was not seen in any tumour studied. Frequently, beta catenin is aberrantly produced in the cytoplasm o f cells in dysplastic naevi and metastatic malignant melanoma, with an impl ied compromise to adhesive function. Furthermore, membranous gamma catenin expression was not seen in any of the 70 melanocytic tumours studied, imply ing obligatory transmembrane binding of cadherins to beta catenin for maint enance of adhesive function. Conclusions-The most important alterations in membranous cadherin and caten in expression are seen late in the biological progression of melanocytic tu mours at the stage of ("in transit") or regional lymph node metastasis, wit h implications for tumour growth, invasion, and dissemination.