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V. Bravo, K. Godeiro, C. Esmerado, D. Faingold, E. Antecka, M.N. Burnier, Jr.; The Immunohistochemical Expression of CCR6 in Primary Human Uveal Melanoma . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2240.
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Chemokines are organ–specific attractant molecules presented in primary tumors that promote tumor homing of metastases to particular distant sites where they bind to a specific ligand. These molecules are also implicated in the cellular transformation, tumor growth, invasion, and in host–tumor response. The CCR6 chemotaxis, associated with the ligand CCL20 located in the hepatic tissue, might be a mechanism by which malignant tumors, such as uveal melanoma (UM) metastasize to the liver. To the best of our knowledge, the expression of CCR6 in primary human UM has not been reported to date.
Twenty–nine specimens of primary human UM were retrieved from the Henry C. Witelson Ocular Pathology Laboratory and Registry (McGill University, Montreal, Canada). The specimens were analyzed regarding histopathological prognostic factors, such as cell type, largest tumor dimension, and tumor infiltrating lymphocytes. Patient’s charters were reviewed to provide clinical information, such as age at diagnosis, follow–up time, previous ocular radiation therapy and presence or not of metastases. Immunohistochemistry was performed using a standard avidin–biotin–peroxidase complex technique, with the rabbit monoclonal anti–CCR6 antibody (Affinity BioReagents, San Francisco, California, USA; diluted 1:50). The immunoreactivity was categorized as positive if any tumor cell displayed distinct staining, irrespective of the staining intensity.
CCR6 was expressed in 79.3% of the specimens. 91.3% of the CCR6 positive tumors were composed of mixed cell type, which was statistically significant (Pearson Chi–Square Tests, p=0.017). There was also an association between CCR6 immunoreactivity and cumulative metastasis. However, this association was not significant (Kaplan–Meier, log–rank test, p=0.08). There was no correlation between the others prognostic factors and CCR6 expression.
The results suggest a new immunohistochemical characterization of UM since CCR6 was expressed in 79.3% of the patients. The correlation between CCR6 expression and mixed cell type may be a consequence of the effect of CCR6 on cellular transformation. Therefore, we hypothesis that CCR6 expression could be responsible for the malignant transformation between differing cell types in UM.
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