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.