Abstract
Purpose :
Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults. The high rate of metastasis, lack of effective systemic therapy and unchanged mortality rate over the last decades demonstrate the need for new therapeutic targets and innovative treatments. ALK inhibitors have been developed as drugs that act on tumors with ALK mutations. Newer generation ALK inhibitors have the potential to target other tyrosine kinases receptors such as ROS1, c-MET, insulin growth factor receptor 1 (IGF-R1), epidermal growth factor (EGFR) and RET. Our goal is to characterize ALK, RET, ROS1, c-MET, EGFR and IGF-R1 expression in UM eyes by immunohistochemistry, and evaluate their association to both clinical and pathological prognostic factors.
Methods :
A total of 24 enucleated eyes from 24 patients with confirmed UM were evaluated. Histopathological characteristics including cell type, degree of pigmentation, lymphocyte infiltration, number of mitotic figures, vascular loops and scleral invasion were analyzed. Clinical characteristics included tumor location, size, development of metastasis and death. Expression of ALK, RET, ROS1, c-MET, EGFR and IGF-R1 was studied by immunohistochemistry of the formalin-fixed, paraffin-embedded samples, which were posteriorly classified according to intensity and extent of staining, in a 0 to 4 score.
Results :
From our sample, ALK was expressed in 10/24 patients (41.6%), RET in 23/24 patients (95.8%), ROS1 in 22/24 patients (91.6%), c-MET in 21/24 (87.5%), EGFR in 13/24 (54.1%) and IGF-R1 in 22/24 (91.6%). ALK and EGFR did not present any score 4 specimens. RET was the most expressed receptor and also had the highest number of score 4 samples, 9/24 (37%); ROS1 had 6/24 (25%) score 4 samples; c-MET had 5/24 (20%) score 4 samples and IGF-R1 2/24 (8.3%). Univariate analysis of score 4 versus score 0,1 and 2 revealed an association with a higher risk of mortality for both RET and ROS (p value= 0.026).
Conclusions :
Our results reveal different degrees of positive staining depending on the receptor. Statistical analysis suggest that higher expression of receptors RET and ROS may be a negative prognostic factor in UM. ALK, RET and ROS1 positivity has never been described in UM literature and highlights these receptors as potential targets for tyrosine kinase inhibitors.
This is a 2020 ARVO Annual Meeting abstract.