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


CONCLUSIONS
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.
National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland.
N
N
Walsh
S
S
Kennedy
A M
AM
Larkin
D
D
Tryfonopoulos
A J
AJ
Eustace
T
T
Mahgoub
C
C
Conway
I
I
Oglesby
D
D
Collins
J
J
Ballot
W S
WS
Ooi
G
G
Gullo
M
M
Clynes
J
J
Crown
L
L
O'Driscoll
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012189:Retrospective Studies
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1