P–glycoprotein as a Marker of Metastasis in Uveal Melanoma

Abstract

Abstract: : Purpose: Despite marked advances in the early clinical detection of uveal melanoma, the ability to accurately predict long–term patient outcome is limited. Several prognostic factors for uveal melanoma have been elucidated. Among them, P–glycoprotein, a transmembrane efflux pump for several chemotherapy agents, has been shown to be adversely associated with patient survival. The purpose of this study is to determine the expression of P–glycoprotein (P–gp) in enucleated specimens of uveal melanoma and to correlate this immunoexpression with the development of metastatic disease in those patients. Methods: Thirty–two cases of enucleated uveal melanoma were obtained from the Henry C. Witelson Ocular Pathology Laboratory of McGill University, Montreal, Canada. Sixteen cases had been treated with radiation prior to enucleation, while the remaining sixteen were enucleated without previous treatment. All cases were immunostained using a monoclonal antibody against P–gp (clone C494). Cases were divided into negative or positive groups depending on whether tumour cell expression of P–gp was below or above 25 percent. Statistical analyses were performed using the Pearson Chi–Square and Student’s T–tests. Results: P–gp was positive in 16 cases (50%), 8 of which had received radiotherapy prior to enucleation. Of the 32 patients, metastasis was observed in 15 patients and of these, 12 had liver involvement, the remaining three had metastatic disease to the bone and lung. From the 16 P–gp positive cases, 11 patients developed metastasis (68.7%). In contrast, of the 16 P–gp negative cases (50%), only 4 patients developed metastasis (25%). A statistically significant association between positive immunostaining for P–gp and metastatic disease was found (p=0.013). No difference was found between the treatment modality and the immuno–expression of P–gp and metastasis. Conclusions: The expression of P–gp in uveal melanoma correlates with the development of metastatic disease in these patients. These findings warrant further in vitro and in vivo investigations of P–gp inhibitors in the treatment of uveal melanoma and its systemic disease.

Keywords: immunohistochemistry • melanoma