Ezrin as a prognostic indicator and its relationship to tumor characteristics in uveal malignant melanoma.
OBJECTIVE
Immunohistochemistry was used to investigate whether uveal malignant melanoma expresses ezrin, a protein involved in cell migration and cell recognition by acting as a linker between the plasma membrane and actin cytoskeleton. Also investigated was whether ezrin immunoreactivity correlates with survival prognosis.


METHODS
A monoclonal antibody, 3C12, that reacts with the carboxyl-terminal part of ezrin was used in retrospective analysis of a population-based cohort of 167 consecutive choroidal and ciliary body melanomas in eyes enucleated from 1972 through 1981, with a median follow-up of 22 years.


RESULTS
Ezrin immunoreactivity in tumor cells was graded negative in 47 (36%) melanomas, positive in 74 (57%), and strongly positive in 9 (7%). The immunoreactivity tended to be homogenous throughout the tumor, with focal concentrations along the cell surface. Positive reaction was significantly associated with high microvascular density (P < 0.001) and presence of macrophages (P < 0.001), but not with tumor size, cell type, or microvascular loops and networks. The 10-year melanoma-specific survival was significantly associated 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 melanoma is associated with higher mortality and with two independent high-risk characteristics: microvascular density and number of infiltrating macrophages. Further experimental studies on the interrelationship of these three factors may shed light on the progression of uveal melanoma and perhaps that of other cancers.
Mäkitie
T
T
Ophthalmic Pathology Laboratory, Department of Ophthalmology, Helsinki University Central Hospital, Finland. teemu.makitie@hus.fi
Carpén
O
O
Vaheri
A
A
Kivelä
T
T
D000911:Antibodies, Monoclonal; D003598:Cytoskeletal Proteins; D015353:Eye Enucleation; D005136:Eye Proteins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000473:pathology; D008545:Melanoma / Q000098:blood supply / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D009389:Neovascularization, Pathologic / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014604:Uveal Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D000099149:Ezrin
D000911:Antibodies, Monoclonal; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D010750:Phosphoproteins; D000099149:Ezrin