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Membrane transport proteins in human melanoma: associations with tumour aggressiveness and metastasis

Walsh, Naomi and Kennedy, Susan and Larkin, Anne-Marie and Tryfanopoulos, Dimitrios and Eustace, Alex and Mahgoub, Thamir and Conway, Catherine and Oglesby, Irene and Collins, Denis and Ballot, Jo and Ooi, Wei and Gullo, Guisipi and Clynes, Martin and Crown, John and O'Driscoll, Lorraine (2010) Membrane transport proteins in human melanoma: associations with tumour aggressiveness and metastasis. Membrane transport proteins in human melanoma: associations with tumour aggressiveness and metastasis, 102 (7). pp. 1157-1162. ISSN 0007-0920

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Abstract

BACKGROUND: Malignant melanoma, generally described as incurable, is notoriously refractory to chemotherapy. The mechanisms contributing to this have not yet been defined and the contributions of drug efflux pumps, implicated in chemo-resistance of many other cancer types, have not been extensively investigated in melanoma. METHODS: In this study, expression of multi-drug resistant (MDR1/P-gp and MRP-1) proteins was examined, by immunohistochemistry, in archival specimens from 134 melanoma patients. This included 92 primary tumours and 42 metastases. RESULTS: On assessing all specimens, MRP-1 and MDR1/P-gp expression was found to be common, with the majority (81%) of melanomas expressing at least one of these efflux pumps. Although there is significant association between expression of these pumps (P=0.007), MRP-1 was found to be the predominant (67% of cases) form detected. chi(2) analysis showed significant associations between expression of MRP-1 and/or MDR1/P-gp and the aggressive nature of this disease specifically increased Breslow's depth, Clark's level and spread to lymph nodes. This association with aggressiveness and spread is further supported by the observation that a significantly higher percentage of metastases, than primary tumours, express MRP-1 (91% vs 57%; P<0.0001) and MDR1/P-gp (74% vs 50%; P=0.010). CONCLUSION: The predominant expression of these pumps and, in particular, MRP-1 suggests that they may be important contributors to the inherent aggressive and resistant nature of malignant melanoma.

Item Type:Article (Published)
Refereed:Yes
Uncontrolled Keywords:malignant melanoma; multiple drug resistance; MDR1/P-gp; MRP-1; immunohistochemistry
Subjects:Medical Sciences > Cancer
DCU Faculties and Centres:Research Initiatives and Centres > National Institute for Cellular Biotechnology (NICB)
Publisher:British Journal of Cancer
Official URL:http://www.nature.com/bjc/journal/v102/n7/full/6605590a.html
Copyright Information:© 2010 Nature Publishing Group.
Use License:This item is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 License. View License
Funders:HEA - Programme for research in third level institutions (PRTLI), Health Research Board, Trinity College Dublin's Start-up funds for new academics 2008/2009, SFI - Molecular Therapeutics for Cancer, Ireland
ID Code:16058
Deposited On:11 May 2011 16:22 by Naomi Walsh. Last Modified 11 May 2011 16:22

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