Ezrin as a prognostic indicator and its relationship to tumor characteristics in uveal malignant melanoma

PURPOSE. Immunohistochemistry was used to investigate whether uveal maligna nt melanoma expresses ezrin, a protein involved in cell migration and cell recognition by acting as a linker between the plasma membrane and actin cyt oskeleton. Also investigated was whether ezrin immunoreactivity correlates with survival prognosis. METHODS. A monoclonal antibody, 3C12, that reacts with the carboxyl-termina l part of ezrin was used in retrospective analysis of a population-based co hort of 167 consecutive choroidal and ciliary body melanomas in eyes enucle ated from 1972 through 1981, with a median follow-up of 22 years. RESULTS. Ezrin immunoreactivity in rumor cells was graded negative in 47 (3 6%) melanomas, positive in 74 (57%), and strongly positive in 9 (7%). The i mmunoreactivity tended to be homogenous throughout the tumor, with focal co ncentrations along the cell surface. Positive reaction was significantly as sociated with high microvascular density (P < 0.001) and presence of macrop hages (P < 0.001), but not with tumor size, cell type, or microvascular loo ps and networks. The 10-year melanoma-specific survival was significantly a ssociated with ezrin immunoreactivity (P = 0.018). After adjustment by Cox regression for tumor size, cell type, microvascular loops and networks, and microvascular density, a clinically meaningful 0.15 difference in 10-year melanoma-specific survival persisted. CONCLUSIONS. The presence of ezrin immunoreactivity in uveal malignant mela noma is associated with higher mortality and with two independent high-risk characteristics: microvascular density and number of infiltrating macropha ges. Further experimental studies on the interrelationship of these three f actors may shed light on the progression of uveal melanoma and perhaps that of other cancers.