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Martina C. Herwig, Chris Bergstrom, Jill R. Wells, Hans E. Grossniklaus; Analysis of Tumor Associated Macrophages in Uveal Melanomas with Class 1 and Class 2 Molecular Profiles. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5248.
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To characterize the type of tumor infiltrating macrophages in uveal melanomas and correlate this with the molecular profile of the tumor.
Patients with uveal melanomas (n=20) were identified and analyzed for clinical and histologic tumor characteristics. These parameters were correlated with the molecular profile (class 1 or class 2). Immunohistochemical stains were performed for CD68-CD163, von Willebrand factor, and Ki67. Statistical analysis was conducted using multivariate analysis of variance and the Pearson test with regard to histologic characteristics, molecular profile, and the type of tumor infiltrating macrophages (M1 versus M2).
In general, molecular class 1 tumors contained more M1 macrophages whereas class 2 tumors contained more M2 macrophages. There was a negative correlation between the number of M1 macrophages and the molecular class (p=0.003) but no statistically significant association with the number of M2 macrophages and molecular profile. There was a statistically significant correlation between the ratio of M2/M1 macrophages and the molecular profile, with a ratio of approximately 1 corresponding to molecular class 1 and a ratio of approximately 2 corresponding to molecular class 2 (p=0.009). Infiltration of macrophages was also significantly associated with the largest basal diameter, the number of mitotic figures, extraocular extension, and the grade of pigmentation.
This study showed that the ratio of M2/M1 macrophages was significantly associated with the molecular profile of uveal melanoma. This observation supports the concept that proangiogenic M2 macrophages are associated with a worse outcome and M1 macrophages are associated with a better prognosis in patients with uveal melanoma.
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