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MT Duffy, JM Harmon, E Tu, T McMahon, Y Wang, CJ Anderson, E Wong, AT Koki; Cyclooxygenase-1 (COX-1), COX-2, and Inducible Nitric Oxide Synthase (iNOS) In Human Choroidal Ocular Melanoma . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1137.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Recent reports strongly imply COX-2 may play distinct roles during oncogenesis, including transformation, tumor proliferation, angiogenesis, metastasis, and immune surveillance. Selective COX-2 inhibitors suppress tumor incidence, growth, and metastasis in models of human cancer. Recently, Denkert et al. reported robust COX-2 overexpression in cutaneous malignant melanoma. In this study, we describe the distribution and expression of COX-1, COX-2, and iNOS in human ocular melanoma. Methods:Twenty-six eyes with medium to large melanomas were randomly retrieved from the University of Illinois eye pathology library under IRB approval. Standard paraffin sections were prepared, blocked for endogenous peroxidase and avidin/biotin, placed in citrate buffer, and stained for COX-1 (#160110, Cayman Chemical), COX-2 (#PG-27, Oxford Biologicals) or iNOS (Pharmacia Corp.). Immunoreactivity was detected using the standard ABC or Envision (Dako) methods, and visualized with the purple substrate VIP (Vector Labs). Non-specific staining was absent in slides incubated with pre-immune, and IgG isotype-matched control anti-sera. Results were read by a minimum of 2 licensed pathologists, with no differences in overall interpretation. Results:COX-1 appears to be constitutively expressed in many normal ocular structures, including ciliary epithelium, retina, optic nerve glial cells, and established vasculature. COX-2 immunoreactivity was not detected in normal ocular structures. COX-2 and iNOS was overexpressed in ≷20% and ≷90% of tumors, respectively. COX-2 is sporadically and focally expressed in epithelioid areas of tumors, infiltrating cells, and vasculature adjacent to and within tumorous lesions. The most intense and diffuse COX-2 staining was observed in a highly aggressive tumor (≷20 mitotic figures per HPF), and in general, appears to be concentrated in proliferating margins of the tumors. iNOS was more consistently and markedly expressed in all stages and grades of ocular melanoma than COX-2. Interestingly, iNOS was also detected in the retinal pigment epithelium, ciliary body, iris pigment epithelium, and ganglion cells in patients who had acquired secondary glaucoma- suggesting iNOS may be induced by increased intraocular pressure. Conclusion:These results provide compelling evidence to further explore whether COX-2 and/or iNOS inhibitors may be clinically useful in patients with ocular melanoma.
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