Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome.
BACKGROUND
Increased levels of P-glycoprotein occur in some osteosarcomas. In this study we determined the relation between P-glycoprotein status and outcome in patients with high-grade osteosarcoma.


METHODS
P-glycoprotein status was determined immunohistochemically in specimens of osteosarcoma of the extremities (stage II) from 92 patients who were treated with surgery and chemotherapy. The P-glycoprotein status was analyzed in relation to the length of event-free survival.


RESULTS
The presence of increased levels of P-glycoprotein in the osteosarcoma was significantly associated with a decreased probability of remaining event-free after diagnosis (P = 0.002). In a multivariate analysis, P-glycoprotein status (P = 0.001) and the extent of tumor necrosis after preoperative chemotherapy (P = 0.04) were independent predictors of clinical outcome. The risk of adverse events was increased substantially (rate ratio, 3.37; 95 percent confidence interval, 1.60 to 7.10) among patients with increased levels of P-glycoprotein in tumor cells, as compared with patients who did not have increased levels of P-glycoprotein in tumor cells.


CONCLUSIONS
In patients with high-grade osteosarcoma treated with surgery and chemotherapy, the presence of increased levels of P-glycoprotein in tumor cells is associated with a significantly increased risk of adverse events and is independent of the extent of necrosis after preoperative chemotherapy.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005121:Extremities; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009336:Necrosis; D012516:Osteosarcoma / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D016016:Proportional Hazards Models
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1