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SA Callejo, AL Caissie, MC Mendez, AM Figueiredo, PM Ozdal, MN Burnier; Cyclooxygenase-2 (COX-2) Expression in Malignant Uveal Melanoma: Its Role in Disease Progression . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1134.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Little is known about the biological mechanisms behind uveal melanoma development and metastasis. Approximately 50% of patients will eventually die of disseminated disease. COX-2 has been investigated in various human malignancies, as it promotes carcinogenesis by facilitating tumor invasion and metastasis. Also, tumor-associated macrophages (TAM) in melanoma have been shown to correlate with poor prognosis. The purpose of the study is to characterize the expression of COX-2 in malignant melanoma cells, correlate this expression with known prognostic factors, and delineate the role of COX-2 positive tumor cells in the progression of uveal melanoma. Methods: One hundred formalin-fixed paraffin embedded cases of uveal melanoma were sent from the American Registry of Ocular Pathology at the Armed Forces Institute of Pathology to the Henry C. Witelson Eye Pathology Laboratory. All cases were immunostained using a monoclonal antibody against COX-2. Cases were divided into 3 groups according to COX-2 tumor cell expression: negative, less than 100 positive cells, and more than 100 positive cells. Slides were also reviewed to determine prognostic factors such as cell type (spindle, mixed, and epithelioid), tumor infiltrating lymphocytes, closed loops, and necrosis. The presence of COX-2 positive TAM was recorded and correlated with COX-2 positive tumor cells. Statistical analysis was performed using binary logistic regression analysis and chi-square test. Results: Of the 100 cases investigated, 57 were positive for COX-2 in malignant cells: 43 cases had less than 100 positive cells and 14 had more than 100 positive cells. In 56 of these 57 cases, COX-2 was also co-expressed in macrophages. This finding was statistically significant (p<0.001). Twenty-three of 32 epithelioid tumors (71.9%) were positive for COX-2 in malignant cells (p<0.04). Twenty-six of 49 mixed tumors (53.1%) and 8 of 19 spindle tumors (42.1%) were positive for COX-2. Ten out of 11 cases with tumor necrosis were positive for COX-2 (p<0.04). Conclusion: Malignant uveal melanoma expresses COX-2 in a limited number of cells. However, this expression is strongly associated with two well-known poor prognostic factors: epithelioid cell tumors and COX-2 positive macrophages. Therefore, the interaction between COX-2 positive tumor cells and COX-2 positive macrophages may play a role in the progression of uveal melanoma.
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