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Multidrug resistance in ocular melanoma
M McNamara1, M Clynes, B Dunne
1Research Foundation, Royal Victoria Eye and Ear Hospital, Dublin, Ireland.
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 gene 1 (MDR1) product (p-glycoprotein) by tumour cells. The purpose of this study was to evaluate the frequency of expression of the MDR1 gene in ocular melanoma whose primary treatment was surgical excision or enucleation.
Methods:
Twelve recent ocular melanomas were received fresh, snap frozen and cryostat sections of tumour were analysed for expression of MDR1 by immunohistochemistry using a well characterised monoclonal antibody to MDR1. Tumour explants were established in short term tissue culture from four tumours and cell blocks were examined by immunohistochemistry.
Results:
MDR1 expression was present in five of 12 ocular melanomas. Upregulation of protein expression was found in four cell lines established in short term culture from tumour explants. A recurrent tumour, initially treated by local excision and radioactive plaque, showed overexpression of MDR1 mRNA.
Conclusions:
These results suggest that significant level of MDR1 may be intrinsically present 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 potential value in planning adjuvant chemotherapy for patients with metastatic disease.
Insights
Multidrug resistance gene 1 (MDR1) is often present in ocular melanoma, contributing to chemotherapy resistance. This suggests MDR1 modulation could be key for treating metastatic ocular melanoma.
Area of Science:
- Ophthalmology
- Oncology
- Molecular Biology
Background:
- Metastatic ocular melanoma exhibits resistance to chemotherapy.
- Multidrug resistance gene 1 (MDR1) expression is a key mechanism for chemoresistance.
Purpose of the Study:
- To determine the frequency of MDR1 gene expression in ocular melanomas.
- To investigate MDR1's role in chemoresistance of ocular melanoma.
Main Methods:
- Immunohistochemistry was used to analyze MDR1 expression in 12 ocular melanoma samples.
- Tumor explants were cultured to assess MDR1 protein upregulation.
Main Results:
- MDR1 expression was detected in 5 out of 12 ocular melanomas.
- Upregulation of MDR1 protein was observed in four cultured cell lines.
- Overexpression of MDR1 mRNA was noted in a recurrent tumor.
Conclusions:
- Ocular melanomas may intrinsically express MDR1, contributing to chemoresistance.
- Targeting MDR1 could be a valuable strategy for adjuvant chemotherapy in metastatic ocular melanoma.