MDR1 gene expression and outcome in osteosarcoma: A prospective, multicenter study

Purpose: Increased expression of the multidrug resistance gene (MDR1) has b een implicated in osteosarcoma prognosis. This study represents the first p rospective assessment. of the prognostic value of MDR1 mRNA expression in p atients with newly diagnosed extremity osteosarcoma. Patients and Methods: A series of patients with high-grade, nonmetastatic e xtremity osteosarcoma were enrolled from six tertiary care institutions and observed prospectively for tumor recurrence (median follow-up duration, 30 months), All patients were treated with (neo)adjuvant chemotherapy and sur gery. Tumors from 123 patients were analyzed for MDR1 mRNA expression. The association of the level of MDR1 expression with the risk of systemic recur rence was examined using survival analyses with traditional and histologic markers as prognostic factors. Results: Using the highest MDR1 value for each patient, a dose-response rel ationship was not identified between the level of MDR1 expression and syste mic relapse (relative risk, 1.15; P =.44). Analyses based on biopsy or rese ction values alone gave similar results (P =.11 and .41, respectively, log rank test). In multivariate analysis, large tumor size (> 9 cm) was the onl y significant independent predictor of systemic outcome (relative risk, 2.8 ; P =.002). Conclusion: We did not identify any correlation between MDR1 mRNA expressio n and disease progression in patients with osteosareoma. It is likely that alterations in other genes are involved in resistance to chemotherapy in os teosarcoma and that they play ct more critical role than MDR1 in this disea se. (C) 2000 by American Society of Clinical Oncology.