Multidrug Resistance Proteins in Primary and Metastatic Soft-tissue Sarcomas: Down-regulation of P-glycoprotein During Metastatic Progression

Abstract

Background: Chemotherapy sensitivity of soft-tissue sarcomas (STS) is limited, which may be due to multidrug resistance (MDR). MDR is associated with expression of Pglycoprotein (P-gp), Multidrug Resistance-associated Protein 1 (MRP1) and Lung Resistance-related Protein (LRP). It is unknown whether in STS metastasis is more resistant than the primary counterpart. Materials and Methods: In 35 chemonaive STS and their metastases (86% chemonaive), MDR proteins were immunohistochemically assessed. Eleven metastases presented synchronously, 24 metachronously. Expression was scored positive (>5% positive tumour cells) or negative. Results: P-gp was positive in 31/34 primaries (91%), versus 22/32 metastases (69%) (p=0.005). This difference was significant for metachronous metastases (p=0.008). MRP1 was positive in 18/32 primaries (56%) and 22/33 metastases (67%). MRP1 was more expressed in synchronous metastases than primaries (p=0.047), but for the overall group this significance disappeared. LRP expression did not differ: 27/34 primaries (80%), versus 28/34 metastases (82%). Conclusion: P-gp, MRP1, LRP expression in the primary tumours was high. Metastatic progression did not coincide with MDRprotein up-regulation.