CD44 expression in melanocytic lesions: a marker of malignant progression?

Abstract

CD44 is the major human cell surface receptor for hyaluronate and functions in a diverse range of physiological processes. Alternative splicing of a single gene generates a family of splice variants (CD44vl-10) in addition to the standard isoform, CD44H. Expression of CD44, particularly CD44v6, has been described to correlate with metastasis formation in various tumours, although evidence in malignant melanoma is inconclusive. In this study, we explored the immunohistochemical pattern of CD44 expression in a range of melanocytic lesions using a panel of monoclonal antibodies raised to CD44H and the variants v3, v4/5, v6 and v8/9. Skin biopsies of 106 lesions from 100 patients were assessed and included benign and dysplastic naevi, melanoma in situ, malignant melanomas in horizontal and vertical growth phase, and cutaneous and lymph node metastases. CD44H was highly expressed in benign and dysplastic naevi and in melanoma in situ. However, expression with melanomas diminished with increasing invasiveness, and the pattern of expression observed correlated significantly with the growth phase of the lesion rather than its Breslow thickness. CD44 splice variants were not detected in any lesions. These results suggest a possible role for downregulation of CD44H in modulating the biological behaviour of malignant melanoma.