title: Clinical significance of P-glycoprotein immunohistochemistry and doxorubicin binding assay in patients with osteosarcoma.
abstract: In 45 osteosarcoma patients, mean age 18 (4-61) years and followed for 14 (5-48) months, we studied the sensitivity to doxorubicin as well as P-glycoprotein expression, and compared these with the extent of tumour necrosis following chemotherapy. Doxorubicin assay was positive in 37 patients in whom necrosis induced by chemotherapy was good in 20 and poor in 17. Metastases developed in nine patients. In eight patients in whom doxorubicin assay indicated tumour resistance, chemonecrosis was poor and all developed pulmonary metastases. P-glycoprotein was studied in pre-treatment biopsies and post-treatment resection specimens. Its expression was positive in 16 patients in whom the necrosis induced by chemotherapy was good in four and poor in 12. In 29 patients with negative P-glycoprotein expression, necrosis was good in 16 and poor in 13. The doxorubicin sensitivity had a high correlation with chemonecrosis (P=0.006) and the incidence of metastases (P<0.001). However, P-glycoprotein expression at the time of diagnosis did not correlate statistically with chemonecrosis (P=0.066). Doxorubicin sensitivity prior to treatment is a better determinant of the response to chemotherapy and clinical outcome than is the P-glycoprotein expression.
authors.affiliation: Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin NT, SAR. sm-kumta@cuhk.edu.hk
authors.forename: S M
authors.initials: SM
authors.lastname: Kumta
authors.forename: Q S
authors.initials: QS
authors.lastname: Zhu
authors.forename: K M
authors.initials: KM
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Griffith
authors.forename: L T
authors.initials: LT
authors.lastname: Chow
authors.forename: P C
authors.initials: PC
authors.lastname: Leung
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000293:Adolescent; D000328:Adult; D001707:Biopsy, Needle; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010020:Osteonecrosis / Q000139:chemically induced; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology*; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D011485:Protein Binding / Q000502:physiology; D012680:Sensitivity and Specificity
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004317:Doxorubicin