Deregulation of the Rb and p53 pathways in uveal melanoma

Uveal melanoma is the most common primary eye cancer, yet its molecular pat hogenesis is poorly understood. In this study, we investigated the immunohi stochemical expression of proteins in the Rb and p53 tumor suppressor pathw ays in 33 uveal melanomas from enucleated eyes. Strong nuclear staining for Rb was present in most tumors. However, a few cases displayed weak nuclear staining and strong cytoplasmic staining (possibly indicating Rb mutation) , and this aberrant staining correlated strongly with failed radiotherapy o r thermotherapy before enucleation. Staining for cyclin D1 was positive in most tumors and was associated with advanced age and larger tumor size, whi ch are both poor prognostic factors. Generally, immunostaining for p53 was weak (suggesting a lack of p53 mutations), although p53 positivity correlat ed strongly with staining for phosphorylated Rb, supporting the notion that inappropriate phosphorylation of Rb can induce p53, Strong immunostaining for MDM2, which can functionally block p53 activity, was observed in most t umors and correlated significantly with female sex. Strong cytoplasmic stai ning was observed for Bc12, which can inhibit both p53-dependent and -indep endent apoptosis, We conclude that Rb and p53 are mutated infrequently in u veal melanoma, but their respective pathways may be functionally inactivate d.