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

Anticancer Res. 2004 Jan-Feb;24(1):291-5.

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 P-glycoprotein (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 MDR-protein up-regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis*
  • Down-Regulation
  • Drug Resistance, Multiple
  • Humans
  • Lymphatic Metastasis
  • Multidrug Resistance-Associated Proteins / biosynthesis*
  • Neoplasm Proteins / biosynthesis*
  • Sarcoma / metabolism*
  • Sarcoma / pathology
  • Sarcoma / secondary
  • Soft Tissue Neoplasms / metabolism*
  • Soft Tissue Neoplasms / pathology
  • Soft Tissue Neoplasms / secondary
  • Up-Regulation
  • Vault Ribonucleoprotein Particles / biosynthesis*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • Vault Ribonucleoprotein Particles
  • major vault protein
  • multidrug resistance-associated protein 1