P-glycoprotein levels predict poor outcome in patients with osteosarcoma

To evaluate the relationship between the expression of P-glycoprotein by os teosarcomas and the rate of metastasis and death, a retrospective review of 172 patients who were diagnosed with osteosarcoma between 1987 and 1992 wa s performed. Forty patients had P-glycoprotein levels available. The majori ty of the osteosarcomas were Stage II-B (33 patients), with the remaining s even being Stage III. Tumor sites included 25 femurs, seven humeri, five ti bias, and one each of pelvis, radius, and fibula. The patients with Stage I II disease at presentation were treated differently from the time of diagno sis and therefore, these seven patients with Stage III osteosarcoma were ex cluded from additional analyses. The expression of P-glycoprotein by cultur ed tumor cells from biopsy specimens was determined using immunofluorescent microscopy. In the 33 patients with Stage IIB osteosarcoma with detectable P-glycoprotein, 67% (10 of 15) had metastases develop as compared with 28% (five of 18) of patients with undetectable P-glycoprotein, Similarly, 53% (eight of 15) of patients with tumors expressing P-glycoprotein died of dis ease compared with 11% (two of 18) with no detectable P-glycoprotein. Expre ssion of P-glycoprotein by tumor cells seems to be associated with an estim ated ninefold increase in the odds of death and a fivefold increase in the odds of metastases in patients,vith Stage IIB osteosarcoma, Kaplan-Meier su rvivorship analysis revealed that patients with detectable glycoprotein far ed worse in terms of survival time and metastasis-free survival. Adjusting for covariates in the Cox proportional hazards model, expression of P-glyco protein and its level were significantly predictive of time to death in pat ients with Stage IIB osteosarcoma.