Expression of multidrug resistance proteins, P-gp, MRP1 and LRP, in soft tissue sarcomas analysed according to their histological type and grade

Komdeur, R; Plaat, B.E.C; van der Graaf, W.T.A; Hoekstra, H.J; Hollema, H; van den Berg, E; Zwart, N; Scheper, R.J; Molenaar, W.M

doi:10.1016/S0959-8049(03)00029-7

« Previous Next »European Journal of Cancer
Volume 39, Issue 7 , Pages 909-916, May 2003

Expression of multidrug resistance proteins, P-gp, MRP1 and LRP, in soft tissue sarcomas analysed according to their histological type and grade

R Komdeur
- Department of Surgical Oncology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
B.E.C Plaat
- Department of Pathology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
W.T.A van der Graaf
- Department of Medical Oncology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
- Corresponding author. Tel.: +31-50-361-28-24; fax: +31-50-361-48-62
H.J Hoekstra
- Department of Surgical Oncology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
H Hollema
- Department of Pathology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
E van den Berg
- Department of Clinical Genetics, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
N Zwart
- Department of Pathology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
R.J Scheper
- Department of Pathology, Free University Hospital, Amsterdam, The Netherlands
W.M Molenaar
- Department of Pathology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands

Received 13 November 2002; accepted 15 November 2002.

Abstract

The biological behaviour of different histological types and grades of soft tissue sarcomas (STS) varies. This might result in a differing sensitivity to cytotoxic drugs. Cross-resistance to functionally and structurally distinct natural-product drugs, known as multidrug resistance (MDR), is associated with the overexpression of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and lung resistance-related protein (LRP). The purpose of this study was to evaluate the expression of P-gp, MRP1 and LRP in STS according to their histological type and grade. In 141 chemotherapy-naive STS patients, the expression of the three MDR proteins was detected by immunohistochemistry. Nine histological types were documented. These were 19% grade 1, 34% grade 2 and 47% grade 3 tumours. Expression of P-gp and LRP was observed more frequently than the expression of MRP1 (P<0.0001). P-gp expression was most pronounced in malignant fibrous histiocytoma (MFH), but was low in leiomyosarcomas. MRP1 was expressed in most malignant peripheral nerve sheath tumours (MPNST). LRP was strongly expressed in MFH and unspecified sarcomas, but was low in liposarcomas. MRP1 and LRP expression was significantly more common in grades 2 and 3 compared with grade 1 tumours. P-gp expression was correlated with MRP1, especially in grade 3 STS. In conclusion, P-gp, MRP1 and LRP are expressed in the majority of STS, but this expression varies according to the histological type. MRP1 and LRP, but not P-gp expression, were found to be correlated to tumour grade. MDR might contribute to the observed differences in clinical behaviour within the heterogeneous group of STS.

Keywords: Multidrug resistance, P-gp, MRP1, LRP, Sarcoma