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Patricia R. Odashiro, Alexandre N. Odashiro, Sebastian Di Cesare, Emilia Antecka, Maria Eugenia Orellana, Miguel N. Burnier Jr; Expression of Hypoxia Inducible Factor-1-α (HIF-1-α) in Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2474.
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Hypoxia Inducible Factor-1-α (HIF-1-α) is a dimeric transcriptional complex primarily recognized for its role in the maintenance of oxygen and energy homeostasis. HIF is expressed under low oxygen conditions in several malignancies, and increases adhesion, proliferation and invasion of neoplastic cells. Moreover, several anti-HIF-1-α drugs have been developed showing anticancer effects by blocking the HIF-1-α pathway. Retinoblastoma (RB) is a highly proliferative tumor that presents hypoxia and necrosis. The objective of this study is to evaluate the expression of HIF-1-α in RB and compare to histopathological prognostic factors.
Twenty-one cases of RB were analyzed. Immunohistochemistry for HIF-1-α was performed using an automated system. The expression was classified according to the intensity (0-3) and percentage (0-3) of positive tumor cells. The scores were summed and a final immunohistochemical score was established for each RB. The immunohistochemical score was compared to histopathological factors (optic nerve, anterior chamber and choroidal invasion, tumor differentiation, and vitreous seeding) and the extent of tumor necrosis.
Histopathologically, 2 cases were well differentiated, 8 moderate and 11 poorly differentiated. Five cases had anterior chamber, 12 had choroidal and 11 had optic nerve invasion. Immunohistochemistry for HIF-1-α was positive in 18 (85.7%) and negative in 3 (14.3%) cases. Six cases had score 2, 1 had score 3, 9 had score 4, and 2 had score 5. There was a significant correlation between the immunohistochemical score and percentage of tumor necrosis (p=0.0091) as well as with vitreous seeding (p=0.0028). There was no significant correlation between HIF-1-α expression and tumor differentiation, optic nerve, anterior chamber and choroidal invasion.
The high expression of HIF-1-α correlated with tumor necrosis and vitreous seeding. This result warrants further investigation to better characterize the mechanism of HIF-1-α expression in RB. Using drugs with low toxicity that target the HIF-1-α pathway can be a possible therapeutic option for RB.
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