P‐glycoprotein expression in osteosarcoma: A basis for risk‐adapted adjuvant chemotherapy

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Abstract
Previous reports on osteosarcomas treated with multi‐agent chemotherapy have shown that P‐glycoprotein expression is a reliable prognostic indicator. The current thinking is that, of the several agents used for the treatment of osteosarcoma, only doxorubicin is involved in drug resistance mediated by P‐glycoprotein. This study examines the relationship of P‐glycoprotein expression to clinical outcome in osteosarcomas, treated only with doxorubicin in addition to surgery, to determine if the prognostic significance of P‐glycoprotein expression reflects the ability of osteosarcoma to respond to this drug. The expression of P‐glycoprotein in tumor specimens was assessed by immunohistochemistry in 37 nonmetastatic, operable osteosarcomas treated at a single institution with doxorubicin as a single adjuvant drug. The P‐glycoprotein status was analysed in relation to the length of event‐free survival. A widespread pattern of P‐glycoprotein expression in tumor cells at diagnosis was significantly associated with a higher rate of systemic relapse (p < 0.001). On comparison of this group of patients with a similar series of 92 patients, all treated with multi‐agent chemotherapy plus surgery of the primary lesion and previously analysed for P‐glycoprotein status, only P‐glycoprotein‐positive, doxorubicin‐resistant tumors consistently benefited from the addition of drugs other than doxorubicin (p < 0.001). Osteosarcomas with different abilities to respond to adjuvant chemotherapy can be identified by the expression of P‐glycoprotein in tumor cells at the clinical onset. P‐glycoprotein status may serve as a basis for risk‐adapted, individualized therapeutic regimens. Standard programs are sufficient for P‐glycoprotein‐negative osteosarcomas, whereas P‐glycoprotein‐positive tumors may benefit from the use of more intensive therapeutic approaches.