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Isabela Vianello Valle, Matthew Kondoff, Alex Laskaris, Tadhg Ferrier, Sabrina Parent, Julia Burnier, Miguel N Burnier; Cancer stem cells markers in primary uveal melanoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):746. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults. Despite effective local treatment, the overall mortality of uveal melanoma is estimated to be around 50%. Previous evidence suggests that tumorigenic and metastatic properties may be attributed to cancer stem cells (CSCs). Various cellular markers have been studied to effectively highlight the presence of CSCs. In this study we aim to characterize the expression of stem cell markers in primary UM using an animal model and enucleated eyes.
Ten enucleated eyes and six eyes of rabbits from the UM animal model were immunostained using antibodies against CD133, Nestin and ALDH, known markers of cancer stem cells. Intensity and distribution of the staining were evaluated using an established score. Intensity was graded from 0 to 2 (negative, mild and intense) and distribution as focal (1) or diffuse (2).
All ten enucleated eyes and six rabbit eyes were positive for at least one marker for CSCs. Thirteen slides (81%) were positive for all three markers. Seven out of ten enucleated eyes and all six rabbit eyes were positive for all three markers. The intensity varied between 1 and 2 in all positively stained lesions. CD133 was detected mainly in cell clusters or in individual cells in rabbit eye tumors, but more diffusely stained in clinical samples. Nestin was positive in all slides and the distribution was mainly focal. Epithelioid cells and cells adjacent to blood vessels appeared to show increased nestin staining, while tumor infiltrating lymphocytes were negative. ALDH was positive with an intensity of 1 in all rabbit samples and in 9/10 patient samples. ALDH staining was reserved to highly positive cells, usually expressed in clusters.
To the best of our knowledge, this is the first study investigating CSCs in both patient enucleated eyes and an animal model. In the clinical and animal model enucleated eyes, Nestin was the best marker for CSCs, followed by CD133 and ALDH. The three markers were positive in the majority of the specimens. The Nestin positivity mainly on epithelioid cells may indicate that Nestin could be used as a prognostic factor. Those three markers should be further investigated as the hallmark of CSCs in a large series of UM enucleated eyes.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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