MULTIDRUG-RESISTANCE IN OCULAR MELANOMA

Aims/background - Metastatic disease in patients with ocular melanoma is resistant to chemotherapy. One of the main mechanisms of modulating multidrug resistance is the expression of the multidrug resistance ge ne 1 (MDR1) product (p-glycoprotein) by tumour cells. The purpose of t his study was to evaluate the frequency of expression of the MDR1 gene in ocular melanoma whose primary treatment was surgical excision or e nucleation. Methods - Twelve recent ocular melanomas were received fre sh, snap frozen and cryostat sections of tumour were analysed for expr ession of MDR1 by immunohistochemistry using a well characterised mono clonal antibody to MDR1. Tumour explants were established in short ter m tissue culture from four tumours and cell blocks were examined by im munohistochemistry. Results - MDR1 expression was present in five of 1 2 ocular melanomas. Upregulation of protein expression was found in fo ur cell lines established in short term culture from tumour explants. A recurrent tumour, initially treated by local excision and radioactiv e plaque, showed overexpression of MDR1 mRNA. Conclusions - These resu lts suggest that significant levels of MDR1 may be intrinsically prese nt in ocular melanomas before exposure to drugs involved in multidrug resistance, and indicate the possible importance of MDR1 in modulating chemoresistance in ocular melanoma. Chemosensitisation may be of pote ntial value in planning adjuvant chemotherapy for patients with metast atic disease.