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Henry A Wood, Pablo Zoroquiain, Patrick Logan, Shawn C Maloney, Nouf AlSaati, Miguel N Burnier; SIRT2 Expression is Higher in Uveal Melanoma Than Ocular Melanocytes. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5059.
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© ARVO (1962-2015); The Authors (2016-present)
Current research has illustrated the potential of Sirtuins to contribute to neoplastic progression in different cancers. SIRT2 is a sirtuin that has been shown to be involved in cell cycle progression and changes in protein acetylation. Uveal Melanoma (UM) is the most common primary intraocular tumour in adults, with 45% of afflicted patients developing metastasis. The aim of this study was to characterize the expression of SIRT2 in UM cases and compare with expression of SIRT2 in the uveal tract of normal human eyes (NHE).
Twenty-one formalin-fixed, paraffin-embedded human UM cases were immunostained for SIRT2, along with 15 NHE obtained from the Eye Bank of Canada. The uveal tract was evaluated in all eyes and tumor-specific staining was evaluated in the UM cases. Immunostaining was graded based on intensity and extent of staining. Intensity was classified as 0 (negative), 1 (weak), 2 (moderate), or 3 (strong). Extent was classified as 0 (negative), 1 (<50% positive cells), 2 (50-80% positive cells), or 3 (>80% positive cells). A final immunoreactive score (IRS) was calculated as follows: intensity x extent. Mean IRS was calculated for each group and differences were evaluated using analysis of variance (ANOVA).
The mean SIRT2 IRS for each cell type in UM cases (+/- standard deviation) was as follows: 4.4 +/- 2.9 for UM cells, 0.9 +/- 0.7 for choroidal melanocytes, and 1.0 +/- 1.7 for iris melanocytes. For NHE, IRS for choroidal melanocytes was 0.5 +/- 0.6. Iris melanocytes were not evaluated due to absence of the anterior segment in those eyes. UM cells had a significantly higher IRS than all groups of evaluated normal melanocytes in both UM and NHE cases (p<0.05). No significant difference in IRS was found when comparing normal melanocytes in UM and NHE cases.
The results of this study demonstrate that SIRT2 expression is significantly stronger in uveal melanoma cells than normal ocular melanocytes. This finding may indicate an important role of SIRT2 as a prognostic marker in uveal melanoma progression.
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