CD44 and variants in melanocytic skin neoplasms

Expression of cell surface molecules that mediate cell-matrix and cell-cell interactions largely contributes to the ability of melanoma cells to migrate and spread beyond the primary site of the tumor. CD44, the principal cell-surface receptor for hyaluronate, and its numerous splice variants have been reported to play a crucial role in invasion and the metastatic process of different human neoplasms, including primary malignant melanoma (PMM). The aim of this study was to clarify which isoforms of CD44 (standard CD44 and CD44 variants) are distributed in PMM with a vertical tumor thickness of >1.4 mm. Staining of CD44 standard (CD44s) and splice variants was further examined for diagnostic and prognostic relevance in a panel of melanocytic skin lesions. Ten cases of PMM with Breslow >1.4 mm were analysed by immunohistochemistry using monoclonal antibodies specific for CD44s and the splice variants v3, v5, v6, v7, v7-8, and v10. In addition, using anti-CD44s, v5, and v6 antibodies, 55 melanocytic lesions, including dermal nevi (n=12), Clark nevi (dysplastic nevi) (CN; n=11), melanoma in situ (Mis; n=8), PMM (n=18), and cutaneous metastasis of malignant melanoma (cMMM; n=6) were assessed. Staining intensities were scored visually and evaluated by means of a staining index. In ten cases of PMM with a Breslow index >1.4 mm positive staining was ascertained for CD44s, v5 and for v6 in three cases. No staining was found for v3, v7, v7-8, and v10. Examination of CD44s, v5, and v6 in 55 melanocytic skin lesions revealed a high index for CD44s in all specimens and a weak staining of v5 in Mis; dermal nevi and CN did not stain for v5. However, in PMM and cMMM we found v5 to be strongly positive. The isoform v6 showed a variable index only in PMM, but without connection to established prognostic criteria. We conclude that CD44s and splice variants can not be regarded as indicators for tumor progression in malignant melanomas. However, v5 may potentially serve as a diagnostic marker for melanocytic skin lesions.