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T.S. Chernin, P.L. Blanco, S.A. Callejo, S. Bakalian, A. Caissie, M.N. Burnier Jr.; Immunohistochemical Evaluation of Migration Inhibitory Factor (MIF) in Uveal Melanoma . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1546.
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Purpose: Migration inhibitory factor (MIF), a proinflammatory cytokine, has been shown both to promote or inhibit tumorigenesis. In lung adenocarcinoma, absence of nuclear expression of MIF was linked with poor prognosis. Although MIF was shown to be expressed in uveal melanoma cell lines, its immune expression has not yet been reported in histopathological specimens obtained from uveal melanoma patients. The aim of this study was to investigate MIF immune expression and intracellular distribution in human uveal melanoma specimens and correlate expression with uveal melanoma prognostic factors. Methods: Thirty human uveal melanoma specimens were formalin-fixed, paraffin-embedded, and immunostained, according to the immunoperoxidase method, using antibodies against MIF. The intracellular location of immunostaining in tumor cells was recorded as cytoplasmic, nuclear, or both. Expression was correlated with cell type, epithelioid or spindle, and presence or absence of tumor infiltrating lymphocytes (TIL). Results:All 30 uveal melanoma specimens showed cytoplasmic immune expression of MIF. Eight specimens (27%) were also found to express MIF in the nuclei. Two of the 19 specimens (10%) classified as epithelioid and 6 of the 11 specimens (54%) classified as spindle co-expressed MIF in both the nuclei and the cytoplasm. Six specimens contained TIL, all of them were epithelioid; and 4 of the 6 did not express MIF in the nuclei. Conclusions: MIF was expressed in both the cytoplasm and the nuclei of human uveal melanoma cells. Absence of MIF expression in the nuclei indeed correlated with poor prognostic factors, namely epithelioid cell type and presence of TIL, suggesting that intracellular localization may play a role in determining the function of MIF, either as a promoter or inhibitor of tumorigenesis.
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