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Debra-Meghan Sanft, Christina Mastromonaco, Ana Beatriz Toledo Dias, Maria Silvia Burnier, Shawn C Maloney, Miguel N Burnier; Expression of SIRT1 in a Uveal Melanoma Animal Model. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4112.
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© ARVO (1962-2015); The Authors (2016-present)
SIRT1 has been previously documented in a variety of malignancies and is believed to inactivate proteins involved in tumor suppression and DNA repair. SIRT1 is expressed in human uveal melanoma. This study aimed to demonstrate that the expression of SIRT1 in a rabbit model is similar to the human pattern and is a reliable way to observe and analyze expression in metastasis.
The rabbit model of uveal melanoma with human uveal melanoma cells injected into the suprachoroidal space used in this study has been previously described. Fourteen formalin-fixed, paraffin-embedded uveal melanoma eyes from rabbits were immunostained using an automated immunostaining protocol and a monoclonal SIRT1 antibody were evaluated. In addition, metastases in either lung or liver for twelve rabbits were analyzed. Scoring was performed as previously reported in human eyes harboring uveal melanoma 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). An immunoreactive score (IRS) was generated by summing the intensity and extent scores. Staining patterns in human and rabbit tumors were compared using the Chi-square test or Spearman's correlation test as appropriate.
Thirteen of 14 (93%) primary choroidal melanomas in the animal model stained positive for SIRT1. Of the positive tumors, 8 (57%) were classified as diffuse and 5 (36%) were considered focal staining. Compared with human studies, no significant difference in the proportion of cases that stained diffusely or focally were seen (P>0.05). Of the 12 metastatic lesions, 6 (50%) were diffuse and 6 (50%) were focal. There was a positive correlation noted between the immunoreactivity score (IRS) of primary tumors compared with the IRS of the metastasis in the same rabbit (r=0.67, P=0.02).
To the best of our knowledge, this is the first time that the immunoexpression of SIRT1 has been evaluated in a rabbit UM model. Furthermore, the expression of SIRT1 in humans and in the rabbit model was similar, which confirms the viability of the human UM cells in the rabbit model as well as the applicability of this model. This study showed that SIRT1 inhibitors may play a role as a new therapeutic target and should be evaluated in the UM animal model.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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