Affiliations: [a] Laboratory of Genetic Toxicology, National Institute of Pediatrics, Mexico City, Mexico | [b] Department of Pediatric Oncology, National Institute of Pediatrics, Mexico City, Mexico | [c] Oncological Surgery Service, National Institute of Pediatrics, Mexico City, Mexico
Correspondence:
[*]
Corresponding author: Araceli Vences-Mejía, Laboratory of Genetic Toxicology, National Institute of Pediatrics, Insurgentes Sur 3700-C Coyoacán, C.P. 04530 Mexico City, Mexico. Tel.: +52 55 10840900 x 1410; E-mail: [email protected].
Abstract: BACKGROUND: Intratumoral up-regulation of genes coding for drug transporters and metabolizing enzymes, such as MDR1 and CYP3A4, after chemotherapy are linked to cancer drug resistance. However their expression in primary soft tissue sarcomas (STS) prior to drug treatment and their role in innate resistance remain unclear. OBJECTIVE: The aim of this study was characterize MDR1 and CYP3A4 expression pattern before to chemotherapy and its clinical implication in pediatric STS. METHODS: In this prospective study we analyzed MDR1 and CYP3A4 mRNA expression in both normal and tumor tissues from 28 newly diagnosed STS pediatric and then compared with patients’ clinical-pathological data, including chemotherapy response. RESULTS: Our data showed that the expression of the MDR1 gene was significantly higher in malignant tissue than in the normal tissues of patients with STS. In addition, high MDR1 expression was significantly associated with local advances, as well as poor response to treatment. In contrast, CYP3A4 expression level was negligible in both tumoral and non-tumoral tissues. CONCLUSIONS: These results suggest that a significant mRNA level of MDR1 gene was intrinsically present in STS before exposure to chemotherapeutic drugs, suggesting that MDR1 may be important contributors of innate chemoresistance of this tumor type.
