Relationship between P-glycoprotein positivity, doxorubicin binding ability and histologic response to chemotherapy in osteosarcomas

We previously reported that the doxorubicin binding ability detected by the doxorubicin (adriamycin) binding assay was closely correlated with the che mosensitivity of human osteosarcomas. In this study, we undertook to clarif y the relationship between P-glycoprotein positivity (%PPG) and doxorubicin binding ability (%DB) in human osteosarcomas in order to determine which i s a mere sensitive index of histologic response to chemotherapy. Ten primar y osteosarcomas were analyzed by the doxorubicin binding assay and by immun ofluorescence to detect cellular P-glycoprotein positivity. Three good resp onders to chemotherapy containing doxorubicin showed a %DB greater than 90% (average: 96.43%), whereas the seven poor responders had values less than 80% (average: 35.31%). The difference between the two groups was statistica lly significant (P = 0.0167). However, the average %PPG of the three good r esponders was 6.73%, whereas the %PPG of the seven poor responders was 14.2 7%. There was no significant difference in %PPG between the two groups (P = 0.3051). No negative correlation between the %DB and the %PPG of all osteo sarcomas (r = 0.536, P = 0.1104) was found, although there was a trend that those tumors with a high %PPG showed a low %DB. These results suggest that osteosarcomas showing a low %DB and %PPG with poor response to chemotherap y, may have multidrug resistance mechanisms other than P-glycoprotein. Ther efore, we conclude that doxorubicin binding ability, which reflects all of the doxorubicin-resistant mechanisms, was more sensitive than P-glycoprotei n positivity in predicting the chemosensitivity of human osteosarcoma. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.