Multidrug resistance gene expression in pediatric primitive neuroectodermal tumors of the central nervous system

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Abstract
Pediatric primitive neuroectodermal tumor (PNET) is a malignancy of the central nervous system currently treated with surgery, radiation therapy, and chemotherapy. Despite aggressive management, tumors recur in almost one-half of all patients. Drug resistance of tumor cells may, in part, explain the poor outcome. Resistance to chemotherapeutic agents may be related to expression of the multidrug resistance gene (MDR1) and its protein product, P-glycoprotein. The role of MDR1 in 16 instances of PNET was investigated using Western blot analysis to detect the expression of P-glycoprotein, messenger ribonucleic acid (mRNA), polymerase chain reaction to detect MDR1 mRNA expression, and Southern blot analysis to assess gene amplification. Analysis of proteins extracted from 15 tumors revealed that two of the 15 patients expressed detectable levels of P-glycoprotein. Polymerase chain reaction of ribonucleic acid from 12 PNET's revealed that six of the 12 patients (four of 10 de novo tumors and both recurrent tumors) expressed MDR1 mRNA. Southern blot analysis of deoxyribonucleic acid from 16 PNET's revealed no evidence of MDR1 amplification in any tumor. This is the first report of MDR1 expression in pediatric brain tumors. These data suggest a possible role for MDR1 in de novo and acquired drug resistance in PNET's.