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R. N. Vianna, B. F. Fernandes, C. Martins, E. Antecka, M. E. Orellana, M. N. Burnier, Jr.; Expression of Sirt1 in Retinoblastoma: A Potential Therapeutic Target. Invest. Ophthalmol. Vis. Sci. 2008;49(13):24.
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SIRT1 is a histone deacetylase protein that regulates cell survival. Recent papers have reported higher endogenous levels of SIRT1 expression in human breast cancer, human colon cancer, human non-melanoma skin cancers, mouse and human prostate cancer, and mouse pulmonary adenocarcinoma. Because SIRT1 may function as a tumor promoter it should be considered as a potential therapeutic target. This study aims to determine the immunoexpression of SIRT1 in retinoblastoma and correlate this expression with histopathological prognostic factors.
Forty-five paraffin-embedded retinobalstomas were collected from the Henry C. Witelson Ocular Pathology Registry, McGill University, Montreal, Canada. The SIRT1 immunostaining was used according to the protocol provided by Abcam Inc. Immunoreactivity was correlated with the presence or absence of invasion into the choroid and optic nerve and the degree of tumor differentiation. Two independent ophthalmic pathologists reviewed all the microslides.
Seven (15.5%) slides were excluded from analysis due to insufficient viable tumor material. Overall, SIRT1 expression was identified in 34/38 (89.5%) specimens analyzed. Three (42.8%) out of 7 tumors without choroidal and/or optic nerve invasion were positive for SIRT1. On the other hand, SIRT1 expression was seen in 30 (96.8%) of the 31 tumors with extra-retinal invasion (p<0.002), 29 (96.7%) of 30 specimens with choroidal involvement (p<0.005), and in all specimens with optic nerve involvement (p<0.02). Ten (77%) of 13 moderate or well differentiated tumors and 24 (96%) of 25 undifferentiated tumors displayed positivity for SIRT1 (p<0.07).
Most of the retinoblastoma specimens in this study expressed SIRT1. The expression of SIRT1 strongly correlated with histopathological features of worse prognosis including optic nerve and choroidal invasion. Our results also suggest that SIRT1 should be considered as a potential therapeutic target for retinoblastoma.
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