Expression of anaplastic lymphoma kinase in uveal melanoma

Abstract

Purpose: The purpose of this study was to determine the expression of anaplastic lymphoma kinase (ALK) in uveal melanoma (UM) to evaluate its potential utility as a therapeutic target. Materials and Methods: A total of 80 formalin-fixed paraffin-embedded enucleated eyes of UM patients, as well as 11 eyes and 11 pulmonary metastases from a rabbit model of human UM, were collected. All samples were stained for ALK using a fully automated immunohistochemical procedure. Human UM cases were classified according to cell type in spindle or epithelioid. Differences in ALK positivity according to cell type were determined using Pearson's Chi-square test. Results: In human UM specimens, ALK was positive in 2 of 39 spindle cell type cases (2.5%) and in 13 of 41 (16.25%) epithelioid cell type cases. The difference in ALK expression between cell types was statistically significant (P = 0.002). In the animal model of human UM cells, all cases (100%) were positive for ALK in both ocular and pulmonary lesions. Conclusion: ALK is expressed in a small proportion of UM, with statistically significant more expression in the more aggressive epithelioid cell type. Furthermore, when ocular tumors and corresponding lung metastasis from a highly metastatic animal model of UM were examined, ALK was positive in all samples. Collectively, our data suggest that ALK expression may be associated with more aggressive tumors. To the best of our knowledge, this is the first demonstration of the potential of ALK as a therapeutic target in human UM, particularly in aggressive tumors.