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A.P. M. Figueiredo, P.C. Ferreira, G.S. Lima; Inducible Nitric Oxide Synthase in Primary Uveal Melanoma Tumors . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3417.
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Purpose: Despite recognition of the malignant potential of human melanomas, the mechanisms responsible for the pathobiological characteristics contributing to tumor growth, cell invasiveness, and distant organ metastasis remain undefined. Recent studies have shown that various human tumors including skin melanoma express an inducible form of nitric oxide synthase (iNOS), which suggests a role of tumor–associated nitric oxide (NO) in tumorigenesis. Also, tumor–associated macrophages (TAM) in melanoma have been shown to correlate with poor prognosis. In this study, we describe the expression of iNOS in human uveal melanoma. The purpose of the study is to characterize the expression of iNOS in malignant melanoma cells and correlate this expression with known prognostic factors. Methods: Twenty standard paraffin sections of primary uveal melanoma tissue specimens were retrieved, prepared and blocked for endogenous peroxidase and avidin/biotin, and immunostained for iNOS. Slides were also reviewed to determine known prognostic factors such as cell type (spindle, mixed, and epithelioid), tumor infiltrating lymphocytes, closed loops and the expression of iNOS was related to these factors. Cases were divided into 2 groups according to iNOS tumor cell expression: negative or positive if at least 20 cells displayed distinct immunostaining. The presence of iNOS positive TAM was recorded and correlated with iNOS expression. Results: Of the 20 cases investigated, 14 tumors (70%) were considered positive for iNOS in malignant cells. In 11 of these 14 cases, iNOS was also co–expressed in macrophages. The expression of this molecule in the tumor strongly correlated with epithelioid (80%, 4 of 5) and mixed cell type (72%, 10 of 14), lymphocytic infiltration (60%, 12 of 20), and vascular loops presence (60%, 12 of 20). Conclusions: Uveal melanoma cells do express iNOS. Our findings suggest that iNOS expression has potential to be linked to local aggressive behavior in human uveal melanomas cells. The role of iNOS in uveal melanoma should be further elucidated, and the use of iNOS inhibitors warrants investigation as adjuvant treatment for this life–threatening malignant disease.
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