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

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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<0.05). Moreover, expression of MRP1 and MDR3 was significantly more frequent in group III and IV tumours as compared with those of groups I and II (p<0.01). After chemotherapy MRP1, MDR3 and, to a lesser extent, P-gp expression was found to be increased in most of the samples. The frequent expression of these MDR-associated proteins in primary tumour cells before chemotherapy and the increase of their levels after chemotherapy, suggest that these proteins play a pivotal role in conferring drug resistance and in producing therapy-induced differentiation on STS.
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Document Type: Research Article

Affiliations: 1: Pathology Department, IRCCS, Ospedale Pediatrico Bambino Gesù, I-00165 Rome, Italy 2: Paediatric Surgery Department, IRCCS, Ospedale Pediatrico Bambino Gesù, I-00165 Rome, Italy 3: Liver Unit, IRCCS, Ospedale Pediatrico Bambino Gesù, I-00165 Rome, Italy 4: Paediatric Haematology/Oncology Department, IRCCS, Ospedale Pediatrico Bambino Gesù, I-00165 Rome, Italy 5: Pediatric Haematology/Oncology Department, University of Padova, I-35128 Padova, Italy

Publication date: January 1, 2012

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  • The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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