P-glycoprotein expression: critical determinant in the response to osteosarcoma chemotherapy.

Abstract

BACKGROUND:

Fewer than 20% of patients with bone cancer who are treated with surgery alone are cured. Even with the best current treatment, surgery combined with chemotherapy, only 60%-80% of patients with nonmetastatic bone cancer and 10% of patients with metastatic bone cancer are cured. Thus far, the reason for treatment failure in the nonresponding subset has not been identified. It has been hypothesized that P-glycoprotein, which confers multidrug resistance, might be the cause. We sought to determine whether the expression of P-glycoprotein is associated with poor treatment outcome in osteosarcoma.

METHODS:

In a retrospective study, we correlated P-glycoprotein expression with the outcome of conventional chemotherapy in 62 consecutive, clinically staged patients diagnosed as having osteosarcoma between 1980 and 1989.

RESULTS:

P-glycoprotein was overexpressed in 27 patients but not in another 34 patients, and expression was ambiguous in the sample from one patient. At a median follow-up of 8.9 years, the 34 patients whose tumors did not express P-glycoprotein had significantly better relapse-free rates than the 27 subjects whose tumors expressed the protein (87% versus 0%; P<.00001) and had improved survival rates (94% versus 35%; P<.00001). Among the 46 patients who received chemotherapy before surgery, the 23 whose tumors were negative for P-glycoprotein showed significantly better long-term outcomes (P<.00002), although differences in tumor necrosis in response to therapy were only of borderline significance (P = .057).

CONCLUSIONS:

P-glycoprotein expression does correlate with treatment failure in patients with osteosarcoma. This correlation raises the possibility that inhibiting the action of P-glycoprotein as part of therapy for this disease would improve outcome.

• Authors: H S Chan, T M Grogan, G Haddad, G DeBoer, V Ling
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 89 Issue 22 Pg. 1706-15 (Nov 19 1997) ISSN: 0027-8874 [Print] United States
• PMID: 9390540 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (biosynthesis, genetics)
• Adolescent
• Adult
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bone Neoplasms (drug therapy, metabolism, surgery)
• Child
• Child, Preschool
• Gene Expression Regulation, Neoplastic
• Humans
• Immunoenzyme Techniques
• Odds Ratio
• Osteosarcoma (drug therapy, metabolism, surgery)
• Prognosis
• Retrospective Studies
• Treatment Outcome