Expression of fibroblast growth factor receptors in naevus-cell naevus and malignant melanoma

In a previous study, we showed by immunohistochemical analysis that basic fibroblast growth factor (bFGF) is expressed strongly and homogeneously in naevus-cell naevus (NCN), while that in malignant melanoma (MM) is heterogeneous and sometimes non-existent. In order to elucidate the role of bFGF in these pigmented tumours, the expression of its receptors must be determined. In this study, we performed an immunohistochemical analysis of FGF receptors 1, 2 and 3 (FGFR-1, FGFR-2 and FGFR-3, respectively) in NCN and MM and compared their expression and localization with those of bFGF. The expression of bFGF and its three receptors was also examined in melanoma cell lines. None of the 10 NCN that showed strong, homogeneous staining for bFGF expressed FGFR-1 or FGFR-3 proteins; six weakly expressed FGFR-2 protein. Ten primary and 10 metastatic MM showed heterogeneous expression for the three receptors, with larger populations of FGFR-3-negative cells in the primary than in the metastatic tumours. Western blot analysis showed homogeneous expression of bFGF protein in all four melanoma cell lines tested, while FGFR proteins had a heterogeneous distribution in the different cell lines. Cultured NCN and normal melanocytes showed no immunoreactive band for FGFR-1 protein, the only protein tested. Our results suggested that tumour-derived bFGF is involved in melanoma formation through an autocrine mechanism, but is involved mostly through a paracrine or other mechanisms in NCN.