Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 10544
© 2008 American Society of Clinical Oncology

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Abstract

MDR1 gene expression and outcome in patients with osteosarcoma

Faculty of Medicine, Zagazig University, Zagazig, Egypt; Faculty of Medicine; Beni-Sweef University, Beni-Sweef, Egypt

10544

Background: Increased expression of the multidrug resistance gene (MDR1) has been implicated in osteosarcoma prognosis. This study represents a prospective assessment of the prognostic value of MDR1 mRNA expression in patients with newly diagnosed extremity osteosarcoma. Methods: A series of 36 patients with high-grade, nonmetastatic osteosarcoma of the extremity were enrolled and observed prospectively for tumor recurrence. All patients were treated with pre- and postoperative chemotherapy and surgery. Preoperative chemotherapy consisted of two cycles of methotrexate (8 g/m2) plus leucovorin calcium (180 mg), cisplatin (120 mg/m2), and doxorubicin (60 mg/m2). Tumors from the thirty-six patients were analyzed for MDR1 mRNA expression Quantitative RT-PCR. The association of the level of MDR1 expression with the risk of systemic recurrence 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 relationship was not identified between the level of MDR1 expression and systemic relapse. In univariate analyses of the other prognostic factors, there was evidence that tumor size and necrosis ( 90% v > 90%) were associated with the risk of systemic relapse and weaker evidence that older patients were more likely to relapse. When all factors were considered in a multivariate model, only tumor size retained a significant relative risk. Conclusions: We did not identify any correlation between MDR1 mRNA expression and disease progression in patients with osteosarcoma. It is likely that alterations in other genes are involved in resistance to chemotherapy in osteosarcoma and that they play a more critical role than MDR1 in this disease.

No significant financial relationships to disclose.

Abstract presentation from the 2008 ASCO Annual Meeting