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AL Caissie, SA Callejo, AM Figueiredo, M Pardo, PM Ozdal, MN Burnier; Cyclooxygenase-2 (COX-2) Expression in Macrophages Infiltrating Uveal Melanoma . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1133.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Recently, it has been shown that a high number of tumor associated macrophages (TAM) in uveal melanoma correlates with poor prognosis, however the biological role of the TAMs has not been elucidated. The aim of this study is to investigate the role of TAMs in uveal melanoma, by characterizing their expression of COX-2, a prostaglandin synthetase that plays a major role in processes such as immunosuppresion, angiogenesis, tumor invasion and metastasis. Methods:One hundred cases of uveal melanoma were received from the American Registry of Ocular Pathology at the Armed Forces Institute of Pathology. The formalin-fixed, paraffin-embedded specimens were immunostained with monoclonal antibodies against CD68 (a macrophage marker) and COX-2. CD68 and COX-2 staining was classified semi-quantitatively as low (L), moderate (M), high (H) or hot spot (HS), with the HS pattern defined as areas of concentrated staining among an otherwise negative to L stain pattern. Slides were reviewed to determine the tumor cell type (spindle, mixed or epithelioid), presence of closed loops, tumor infiltrating lymphocytes (TIL) and necrosis. Statistical analysis was performed using the ordinary least squares regression test. Results:Nineteen of 100 cases were classified as macrophage (CD68) L, 16 were CD68 M, 48 were CD68 H and 17 were CD68 HS. Seventy percent of cases were COX-2 positive in TAM: 23 were COX-2 L, 10 were COX-2 M, 6 were COX-2 H and 31 were COX-2 HS. Of the 70 COX-2 positive cases, 5 were macrophage (CD68) L, 9 were CD68 M, 45 were CD68 H and 12 were CD68 HS. There was a linear relationship (p<0.001) between the number of TAM and COX-2 positive macrophages. Nineteen of 100 cases were classified as spindle, 49 as mixed and 32 as epithelioid. Of the highly COX-2 positive tumors (H and HS) 86% were mixed or epithelioid. Twenty-five of 100 cases had closed loops, 37 had TIL, and 11 had necrosis. TAMs associated with necrosis were COX-2 negative. Conclusion:Tumor associated macrophages were found to express COX-2 in the majority of uveal melanoma cases and the higher the number of macrophages present in the tumor, the higher the expression of COX-2. By expressing COX-2, uveal melanoma macrophages may enhance the invasive and metastatic potential of uveal melanoma cells, thereby correlating with poor prognosis.
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