Multidrug resistance proteins in primary and metastatic soft-tissue sarcomas: Down-regulation of P-glycoprotein during metastatic progression

Background: Chemotherapy sensitivity of soft-tissue sarcomas (STS) is limited, which may be due to multidrug resistance (MDR). MDR is associated with expression of P-glycoprotein (P-gp), Multidrug Resistance-associated Protein I (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 31/34primaries (91%), versus 22132 metastases (69%) (p=0.005). This difference was significant for metachronous metastases (p = 0.008). MRP1 was positive in 18132 primaries (56%) and 22133 metastases (670%). 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 primanes (80%), versus 28134 metastases (82010). Conclusion: P-V, MRP1, LRP expression in the primary tumours was high. Metastatic progression did not coincide with MDR-protein up-regulation.