Expression of multidrug resistance-associated proteins in paediatric soft tissue sarcomas before and after chemotherapy

Arianna Citti, Renata Boldrini, Alessandro Inserra, Anna Alisi, Rosanna Pessolano, Angela Mastronuzzi, Angelica Zin, Luigi De Sio, Angelo Rosolen, Franco Locatelli, Doriana Fruci

Research output: Contribution to journalArticle

Abstract

Expression of multidrug resistance (MDR) proteins is thought to significantly contribute to the different biological/clinical behaviour of soft tissue sarcomas (STS) of various histological types and clinicopathological stages, as they are responsible for active efflux of cytotoxic drugs from tumour cells. We investigated the expression of 3 MDR proteins, i.e., permeability glycoprotein 1 (P-gp), multidrug resistance-associated protein 1 (MRP1) and multidrug resistance 3 (MDR3), in 43 STS specimens from newly-diagnosed paediatric patients, 31 with rhabdomyosarcoma (RMS) and 12 with non-RMS STS. To assess the influence of chemotherapy on STS drug resistance, the number of MDR-associated protein-positive cells was determined in 15 patients on both primary lesions before chemotherapy and on residual tumour after chemotherapy. At least one of the MDR-associated proteins tested was detected in 84% of primary untreated STS specimens. In these specimens, MRP1 was detected in a high percentage (70%) of the cases, followed by MDR3 in 58% and P-gp in 44%. Many specimens showed co-expression of two different MDR proteins. Interestingly, MDR3 was significantly associated with the presence of PAX3/PAX7-FKHR transcripts in RMS (p

Original languageEnglish
Pages (from-to)117-124
Number of pages8
JournalInternational Journal of Oncology
Volume41
Issue number1
DOIs
Publication statusPublished - Jul 2012

Keywords

  • Chemotherapy resistance
  • Multidrug resistance
  • Multidrug resistance-associated proteins
  • Paediatric tumours
  • Soft tissue sarcomas

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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