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Paulina Garcia de Alba Graue, Alicia Goyeneche, Jacqueline Coblentz, Tadhg Ferrier, Miguel N Burnier; Expression of cysteinyl leukotriene receptors 1 and 2 in uveal melanoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):757. doi: https://doi.org/.
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Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and expresses frequent driver mutations in GNAQ and GNA11 genes, both of which are activated by the cysteinyl leukotriene receptor 2 (CYSLTR2) and are downstream effectors of MAPK/MEK/ERK signaling pathway. Overexpression of cysteinyl leukotriene receptors are linked with cancer processes such as neoangiogenesis, sustained proliferative signaling, migration and invasion. The aim of this study is to analyze the expression both CYSLTR1 and CYSLTR2 and further investigate their potential as therapeutic targets in UM.
In total, 10 UM were evaluated. Immunohistochemistry was performed using the Ventana Benchmark Automated Platform on paraffin-embedded samples using polyclonal anti-CYSLTR1 and polyclonal anti-CYSLTR2 antibodies. Slides were digitized using the Aperio Scanscope Scanner. Expression was evaluated using an Immunoreactive Score as follows: intense cytoplasm staining in malignant cells (2+); mild staining in the cytoplasm of malignant cells (1+), no staining in the cytoplasm of malignant cells (0), and further subclassified by the extent of staining as localized (1+) or diffuse (+2). Statistical analysis was performed using Fischer’s Exact Test; P<0.05 was considered significant.
CYSLTR1 expression was positive in all 10 UM. In 8 UM (80%), the score was 2-4, while a score of 0-1 was obtained in 2 UM (20%). CYSLTR2 expression was positive in 9 samples of UM. In 6 UM (60%), the score was 2-4, while a score of 0-1 was obtained in 4 UM (40%). The extent of both CYSLTR1 and CYSLTR2 expression was predominantly localized (~60%). The normal uveal tract scored 0-1 in 8 samples, and a score of 2-4 in 2 samples. Both CYSLTR1 (P=0.023) and CYSLTR2 (P=0.0108) expression in UM was statistically higher when compared to the normal uveal tract. A tendency of intense staining of both CYSLTR1 and CYSLTR2 in the areas where the number of infiltrating melanophages was higher was also observed.
To the best of our knowledge, this is the first study to analyze the expression of both CYSLTR1 and CYSLTR2 in UM. Our study demonstrates that both CYSLTR1 and CYSLTR2 expression is statistically significant in UM when compared to the normal uveal tract, thus supporting their association in the malignant transformation of this tumor. Further investigation of CYSLTRs as potential therapeutic targets in UM is warranted.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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