Purchase this article with an account.
Juliana Portela Passos, Ana Beatriz Toledo Dias, Pablo Zoroquiain, Christina Mastromonaco, Sarah Alghamdi; Sirtuin 2 expression in uveal melanoma correlates with metastasis in an animal model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5334.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Sirtuins (Sirt) are a family of seven enzymes that are involved in the cell cycle. Previous studies have shown that Sirt2 acts both as a tumor suppressor and as an oncogene. In uveal melanoma, we have shown that Sirt2 is preferentially expressed in malignant, but not in normal, uveal melanocytes. The purpose of this study was to analyze Sirt2 expression in primary tumors and metastases from an animal model of uveal melanoma.
The rabbit model of uveal melanoma with human uveal melanoma cells injected into the suprachoroidal space used in this study has been previously described.<br /> Seventeen formalin-fixed, paraffin-embedded uveal melanoma eyes from the rabbits were immunostained for Sirt2 and were analyzed. In addition, three lung metastases were all stained and scored. Immunostaining was scored based on the intensity and distribution of the immunoreaction. Intensity was classified as 0, 1, 2, or 3, which corresponds to negative, weak, moderate, or strong staining, respectively. Extent was classified as 0 for negative, 1 for less than 50% positive cells, 2 for cells with positivity between 50% to 80%, or 3 for cells with >80% positivity. A total immunoreactive score (IRS) was then generated by multiplying intensity by extent.
Sirt2 was expressed in 14 of 17 primary uveal melanoma tumors analyzed with an average IRS of 1.71. Three of these animals also had metastases, which had a mean IRS of 2.33. The difference in Sirt2 staining was not statistically different between the primary tumors and metastases (P>0.05). We also compared the IRS in primary tumors from rabbits that did not have metastases (n = 14; IRS = 1.93) to those animals that had metastases (n = 3; IRS = 0.67; P = 0.19).
Primary tumors that generated metastases had a higher expression of Sirt2 than tumors that did not metastasize. Moreover, metastastic uveal melanoma showed higher expression of Sirt2 than primary tumors. These results strongly suggest that Sirt2 acts as an oncogene in this uveal melanoma animal model. Although our data did not reach statistical significance, this may be a consequence of the limited number of metastases investigated. Future studies are warranted to confirm these findings in human ocular tumors and metastases.
This PDF is available to Subscribers Only