Effects of proton beam irradiation on uveal melanomas: a comparative study of Ki-67 expression in irradiated versus non-irradiated melanomas

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Abstract
AIMS To assess the cellular proliferation using the monoclonal antibody Ki-67, in paraffin embedded uveal melanomas irradiated by proton beam, as well as in non-irradiated uveal melanomas. METHODS 30 enucleated eyes were included for histopathological study and Ki-67 immunostaining. Patients were enucleated between 1991 and 1996 for uveal melanoma, 14 after proton beam irradiation and 16 without treatment (control group). The mean follow up period was 2.5 years after diagnosis and 1 year after enucleation. RESULTS A significant relation was found between Ki-67 score and mitotic index (r = 0.56, p = 0.001), histological largest tumour diameter (r = 0.38, p = 0.03), fibrosis (r = −0.35, p = 0.05), absence of tumoral pigmentation (p = 0.05), and presence of vascular thrombosis (p = 0.03). The Ki-67 score was significantly higher in the non-irradiated group (p = 0.01) and in the group of patients whose cause of enucleation was tumoral evolution (p = 0.005) compared with the group of patients enucleated after neovascular glaucoma. The Ki-67 score was very high in a case of orbital recurrence of uveal melanoma and metastatic death. 70% of metastasised tumours showed a Ki-67 score higher than the median value. CONCLUSION Ki-67 labelling is a reliable method of estimating the proliferative activity in uveal melanomas after proton beam irradiation. The Ki-67 score is significantly correlated with prognostic variables (mitotic index and histological largest tumour diameter), and with radiation effects after proton beam irradiation.