MDR1 gene expression and outcome in osteosarcoma: a prospective, multicenter study.
OBJECTIVE
Increased expression of the multidrug resistance gene (MDR1) has been implicated in osteosarcoma prognosis. This study represents the first prospective assessment of the prognostic value of MDR1 mRNA expression in patients with newly diagnosed extremity osteosarcoma.


METHODS
A series of patients with high-grade, nonmetastatic extremity 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 surgery. Tumors from 123 patients were analyzed for MDR1 mRNA expression. 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 (relative risk, 1.15; P =.44). Analyses based on biopsy or resection values alone gave similar results (P =.11 and.41, respectively, log rank test). In multivariate analysis, large tumor size (> 9 cm) was the only significant independent predictor of systemic outcome (relative risk, 2.8; P =.002).


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.
Wunder
J S
JS
Samuel Lunenfeld Research Institute and the University Musculoskeletal Oncology Unit, Mount Sinai Hospital, Toronto, Ontario, Canada. wunder@mshri.on.ca
Bull
S B
SB
Aneliunas
V
V
Lee
P D
PD
Davis
A M
AM
Beauchamp
C P
CP
Conrad
E U
EU
Grimer
R J
RJ
Healey
J H
JH
Rock
M J
MJ
Bell
R S
RS
Andrulis
I L
IL
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002648:Child; D018450:Disease Progression; D015870:Gene Expression; D019450:Genes, MDR; D006801:Humans; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
D012333:RNA, Messenger