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Silvin Bakalian, Dana Faingold, Pablo Zoroquiain, Matthew Balazsi, Natàlia Vilà, Emilia Antecka, Miguel N Burnier; The expression of FoxC1 in Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5057.
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Forkhead box transcription factor C1 (FoxC1) plays an important role in the eye differentiation. FoxC1 overexpression was linked to poor survival in hepatocellular carcinoma and breast cancer. Other reports showed decreased metastasis of breast cancer cells following FoxC1 overexpression. The aim of this study is to evaluate the expression of FoxC1 inuveal melanoma (UM).
Fifty one cases of paraffin-embedded, human UM were immunostained with a polyclonal FoxC1 antibody. Immunohistochemical expression was assessed based on staining extent and intensity. Extent was evaluated as the percentage of cells showing positive staining (0=none, 1= ≤50% of the tumour cells; 2=51-75% of the tumor cells; and 3=≥76% of the tumor cells). Staining intensity was assessed as follows (0=none; 1=weak; 2=moderate; and 3=strong). The cases were grouped into low FoxC1 expression when combined extent and intensity scores were between 1 and 4, and high FoxC1 expression when total score was 5 and 6. Clinical-pathological data were obtained, including age, gender, cell type, and largest tumor dimension (LTD), which were correlated with FoxC1 expression.
The expression of FoxC1was positive in all cases of UM samples (51 specimens). The immunostaining was always cytoplasmic. In addition, weak intranuclear staining was seen in 16 cases. Twenty specimens showed low FoxC1 expression, while 31 specimens showed high FoxC1 expression. The mean age of UM patients was 62 years, and the mean follow up period was 52 months. The mean LTD was 11mm. There were 8 (16%) cases of spindle UM, 26 (51%) cases of mixed UM and 17 (33%) cases of epithelioid cell type UM. All intratumoral vessels as well as retinal and choroidal vessels displayed negative immunostaining for FoxC1. Survival analysis did not show statistically differences between the two groups of patients (low expression of FoxC1 versus high expression of FoxC1). However, there was a trend with a longer survival rate for the group of patients with low expression of FoxC1.
To the best of our knowledge this is the first study on the expression of FoxC1 in primary uveal melanoma. A positive correlation of intranuclear staining with metastasis has been reported in other malignancies. Due to the fact that FoxC1 is expressed in the cytoplasm of uveal melanoma cells, it is possible that FoxC1 plays a different role in this particular malignancy.
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