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B. F. Fernandes, D. Faingold, E. Antecka, C. Martins, S. Bakalian, M. N. Burnier, Jr.; Phosphorylated Fak Is Expressed in Primary Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2008;49(13):73. doi: https://doi.org/.
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Focal Adhesion Kinase (FAK) is a cytoplasmic tyrosine kinase that plays a central role in several cellular mechanisms such as differentiation, migration and regulation of cell cycle. The activation of FAK is initiated by the phosphorylation at Tyr397. FAK is commonly overexpressed in different cancers including prostate, thyroid, colorectal, ovarian and skin melanoma. Previous in vitro studies showed that the activation of FAK promotes an aggressive melanoma phenotype. The purpose of this study is to investigate the expression of FAK in Uveal Melanoma (UM) and correlate with prognostic factors and metastatic dissemination.
Thirty-nine cases of paraffin-embedded human UM were immuno-stained with a FAK Phosphospecific monoclonal antibody (Anti-FAK[pY397], BioSource International Inc., USA) using the Ventana BenchMark fully automated machine (Ventana Medical Systems, Tucson, AZ). The immuno-staining was evaluated in a semi-quantitative method based on the extent and intensity of the staining. Clinical-pathological data were obtained, including age, gender, cell type, and largest tumor dimension and further correlated with FAK expression. The survival rates of patients were also assessed using a Kaplan-Meier test. Additionally, cytospins of five UM cell lines (92.1, OCM-1, MKTBR, UW1 and SP6.5) were immunostained for the expression of FAK[pY397].
The expression of FAK[pY397] was positive in 34 (87.2%) specimens. Staining pattern was diffuse in 26 (66.7%) and focal in 8 (20.5%) cases. High and low intensity of expression was seen in 29 (74.4%) and 5 (12.8%) samples, respectively. No correlation with survival was seen in the Kaplan-Meir analysis, neither with other prognostic factors. In the cytospins, expression was high for SP6.5, low for 92.1 and negative for the least aggressive cell lines OCM-1, MKT-BR and UW-1.
To the best of our knowledge this is the first study on the expression of FAK in primary human UM. The presence of the phosphorylated form of FAK was seen in a high percentage of cases. Possibly due to the high positivity rates in the cohort studied, a correlation with survival and prognostic factors was not statistically significant. The staining of the cell lines revealed that the most aggressive cell lines expressed the Phosphorylated form of FAK. Phosphorylation of FAK activates migration and invasion of neoplastic cells, which are important steps in the metastatic cascade. Our results warrant further studies on anti-FAK therapies in UM.
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