Receptors for the Liver Synthesized Growth Factors IGF–1 and HGF/SF in Uveal Melanoma. Intercorrelation and Prognostic Implications

Abstract

Abstract: : Purpose: Uveal melanoma disseminates preferentially to the liver. The reason for this homing is largely unknown, but growth factors synthesized in the liver may be implicated. Here we investigated the possible relationship between cell surface receptors for two such growth factors; the c–Met proto–oncogene that constitutes the receptor for hepatocyte growth factor / scatter factor (HGF/SF); and the insulin–like growth factor 1 receptor (IGF–1R). Also, their role as prognostic factors was aimed to be clarified. Methods: Paraffin–embedded tumor specimens from 132 patients with primary uveal melanoma were analyzed using well–established specific antibodies against c–Met and IGF–1R. The intercorrelation of receptor expression and association with melanoma–related survival of patients were determined using univariate and multivariate analyses. Results: While the expression of both IGF–1R and c–Met was significantly associated with melanoma–specific mortality by univariate analysis, only IGF–1R showed independent prognostic value. The prognostic value of IGF–1R was stronger than currently used prognostic parameters like tumor cell type and tumor diameter. The expression patterns of the two growth factors receptors were weakly intercorrelated. Conclusions: Our data suggest that the receptors for IGF–1 and HGF/SF may play a role in the spread of uveal melanoma and its affinity to the liver. The strong correlation between IGF–1R expression and melanoma–specific mortality points to the use of IGF–1R as a prognostic tool. Furthermore, our study highlights the possibility to use IGF–1R inhibitors as a new therapeutic option for patients with uveal melanoma.

Keywords: melanoma • growth factors/growth factor receptors • immunohistochemistry