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Expression of multidrug resistance proteins, P-gp, MRP1 and LRP, in soft tissue sarcomas analysed according to their
R Komdeur1, B E C Plaat, W T A van der Graaf
1Department of Surgical Oncology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
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.
Insights
Multidrug resistance proteins P-glycoprotein (P-gp), MRP1, and LRP are expressed in soft tissue sarcomas (STS). Their expression varies by histological type and grade, potentially influencing treatment resistance.
Area of Science:
- Oncology
- Pathology
- Molecular Biology
Background:
- Soft tissue sarcomas (STS) exhibit diverse biological behaviors, influencing sensitivity to chemotherapy.
- Multidrug resistance (MDR), characterized by cross-resistance to natural-product drugs, is often linked to P-glycoprotein (P-gp), MRP1, and LRP overexpression.
Purpose of the Study:
- To investigate the expression patterns of P-gp, MRP1, and LRP in various STS histological types and grades.
- To determine if MDR protein expression correlates with STS classification and tumor grade.
Main Methods:
- Immunohistochemistry was employed to detect P-gp, MRP1, and LRP expression in 141 chemotherapy-naive STS patients.
- Nine distinct histological subtypes of STS were analyzed.
- Tumor grading (1, 2, and 3) was assessed for all samples.
Main Results:
- P-gp and LRP expression were more prevalent than MRP1 across all STS subtypes.
- Specific expression patterns were observed: P-gp highest in MFH, low in leiomyosarcomas; MRP1 common in MPNST; LRP high in MFH and unspecified sarcomas, low in liposarcomas.
- MRP1 and LRP expression significantly increased with higher tumor grades (2 and 3) compared to grade 1. P-gp correlated with MRP1, particularly in grade 3 STS.
Conclusions:
- P-gp, MRP1, and LRP are frequently expressed in STS, with expression profiles varying by histological type.
- MRP1 and LRP expression correlate with STS tumor grade, suggesting a role in disease progression.
- Differential expression of these MDR proteins may contribute to the varied clinical behavior observed in STS.
