QUANTITATIVE-ANALYSIS OF MULTIDRUG-RESISTANCE GENE-EXPRESSION IN HUMAN OSTEOSARCOMAS

We evaluated the MDR1 expression levels in 77 osteosarcomas and invest igated whether MDR1 mRNA expression in osteosarcomas varies with locat ion within the tumour, following chemotherapy, or after metastasis. We modified the semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) assay to determine accurately the levels of MDR1 mRN A expression in clinical specimens. We show that specimens collected f rom multiple locations in six tumours revealed very little variation i n MDR1 expression suggesting that the levels of MDR1 in these rumours do not vary greatly with location within the tumour mass. In a compari son of pre and post-chemotherapy specimens it was found that MDR1 leve ls did not change appreciably following chemotherapy in 16 of 20 cases . In addition, in eight of ten specimens obtained before and after met astasis, the amount of MDR1 mRNA was found to remain relatively consta nt despite metastatic spread. Thus, many osteosarcomas exhibited intri nsic expression of MDR1 mRNA before multidrug regimens which invariabl y included doxorubicin and, in most cases, MDR1 expression was not ind uced following chemotherapeutic treatment. Our results suggest that so me osteosarcoma patients may have primary tumours which are resistant to doxorubicin. These individuals may benefit from different chemother apeutic regimens, e.g. the addition of MDR reversal agents.