Immunohistochemical findings and proliferation markers in uveal melanomas after gamma‐knife radiosurgery

Abstract

Abstract Purpose We describe immunohistochemical characteristics and tumor cell proliferation in 12 eyes with uveal melanoma enucleated after Gamma‐Knife radiosurgery (GKR) with different treatment doses. Methods Tumors were stained for the specific melanocytic markers S‐100, HMB‐45 and Melan A. The immunoreactive score (IRS, Remmele‐score) was calculated from percentage of positive cells and staining intensity. Proliferating cells were identified with PC‐10 and MIB‐1 staining and counted. All markers were evaluated at the tumor apex, center, base and margins. Results were compared between eyes enucleated for tumor recurrence or treatment related side effects. Influence of treatment dose and time to enucleation were analyzed. Results Only 1 of 12 melanomas stained positive for S‐100 (median IRS 0). HMB‐45 and Melan A were both positive in 11 of 12 cases (median IRS 9 and 10.5, respectively). Staining intensity was higher at the tumor apex, base and margins than in the tumor center, which frequently showed necrosis. PC‐10 and MIB‐1 showed proliferating cells in all melanomas, without relation to tumor recurrence (n=5), radiation dose (25‐50 Gy) or time between GKR and enucleation (1‐47 months). We found markedly more proliferating cells at the tumor margins. Conclusion Proliferating cells were found even in cases with clinically stable disease. The finding of cycling cells at the tumor margins and necrosis in the tumor center might reflect the inhomogenous dose distribution used for GKR, with the tumor center receiving almost twice the dose of the surface and margins. It might also be an indicator for an intrinsically higher proliferation rate at the margins of the melanoma.