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H. R. Oltean, S. C. Maloney, E. Antecka, M. E. Orellana, B. F. Fernandes, M. N. Burnier, Jr.; Expression of SIRT1 in Primary Human Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3381.
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SIRT1 is the mammalian orthologue of yeast Sir2 (silent information regulator 2), an NAD+-dependent histone deacetylase. SIRT1 has been shown to play a role in biological processes including tumorigenesis, embryogenesis and angiogenesis. To date, the role of SIRT1 in human uveal melanoma (UM) remains unknown. The aim of our study is to investigate the expression of SIRT1 in primary human uveal melanomas.
Formalin-fixed, paraffin-embedded sections from 19 enucleated eyes of UM patients were evaluated. Inclusion criteria consisted of a minimum follow-up of 60 months for patients without metastases and sufficient material for immunohistochemical analysis. SIRT1 expression was investigated using a rabbit anti-human monoclonal antibody. Sections of prostate cancer were used as positive controls. Expression of SIRT1 was evaluated in all primary choroidal melanomas and was scored in the following manner: Extent: Negative, Focal (<40% staining positive), or Diffuse (≥40% staining positive); Intensity: 0 (negative), 1 (mild staining), or 2 (strong staining). Additionally, SIRT1 expression was investigated in other ocular tissues including retinal pigment epithelium (RPE), retina, iris, ciliary body, cornea and limbus.
Twelve of 19 (63%) primary choroidal melanomas stained positive for SIRT1. Expression of SIRT1 was predominantly cytoplasmic. Of the positive sections, 6 (50%) were classified as diffuse and 6 (50%) were classified as focal, all of which had mild staining intensities. Three of the 12 (25%) cases that stained positive were from patients diagnosed with metastasis, while 5 of the 7 (71%) negative cases were from patients diagnosed with metastasis. These results were not statistically significant (p = 0.074). Additionally, all cases except for two showed positive staining in the non-pigmented epithelial cells of the ciliary body. Staining was negative in the retina and iris in all cases, while positivity was frequently seen in the limbus (7 of 11 cases) and rarely in RPE (4 of 19 cases) and the corneal epithelium (1 of 12 cases).
To the best of our knowledge, this is the first time that the immunoexpression of SIRT1 has been demonstrated in human uveal melanoma. The majority of tumors express SIRT1, however, patients with tumors that were negative for SIRT1 expression developed metastasis at a greater rate than those with SIRT1 expression. This is contrary to the expression of SIRT1 in other cancers in which the upregulation of this deacetylase correlates with metastasic disease. Further research with a larger case series should be performed to gain a better understanding of the role of SIRT1 in UM.
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