Abstract
Purpose :
Uveal melanoma (UM) is a disease that affects approximately five people per million in the United States. This disease metastasizes predominantly to the liver, and treatment options following clinical detection of these sequelae are limited. Anaplastic lymphoma kinase (ALK) is a transmembrane receptor kinase that belongs to the insulin receptor superfamily and has previously been shown to play a role in cell proliferation, migration and invasion in several malignant tumors, including lymphoma, non-small cell lung cancer, and skin melanoma. The purpose of this study was to determine the expression of anaplastic lymphoma kinase (ALK) in UM in order to evaluate its potential utility as a therapeutic target.
Methods :
Eighty formalin-fixed paraffin-embedded enucleated eyes of patients with UM, 11 eyes from a rabbit model of UM, and 11 pulmonary metastasis from this model were collected from the Henry C. Witelson Ocular Pathology Laboratory, McGill University, Montreal, Canada. All samples were stained for ALK using a fully-automated immunohistochemical procedure. The presence of ALK was confirmed for any tumors that showed positive expression. Human UM cases were classified according to cell type: spindle or mixed (predominantly 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 spindle cell type cases (2.5%) and in 13 (16.25%) mixed cell type cases. The difference in ALK expression between cell types was statistically significant (P=0.02). Regarding the animal model, in which all animals were inoculated with mixed cell type tumors, all cases (100%) were positive for ALK in both primary and pulmonary lesions.
Conclusions :
ALK is expressed in the minority of human eyes with UM, with statistically greater expression in the more aggressive, mixed cell type. ALK is also expressed in all primary UMs and pulmonary metastasis in an established, highly metastatic animal model of UM. Therefore, our data suggest that ALK expression is more prevalent in aggressive tumors. To the best of our knowledge, this is the first demonstration of ALK’s potential as a therapeutic target in human UM, and in particular aggressive tumors.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.