P-glycoprotein expression in high grade central osteosarcoma and normal bone cells. An immunohistochemical study.
One important mechanism by which multidrug resistance is mediated is the mdr1 gene product, P-glycoprotein (Pgp). Even though chemotherapy, in the treatment of high grade central osteosarcoma (hgc-OS), has led to dramatic improvements in survival rate, a certain percentage of patients still show only a poor response to chemotherapy. To further characterize a potential connection between Pgp and chemotherapy as well as the role of Pgp in tumorigenesis of osteosarcoma, we analyzed Pgp-expression in hcg-OS. Immunohistochemistry was performed on 68 hgc-OS samples from 58 patients using the monoclonal antibody JSB-1; in addition, Pgp-expression in normal bone cells was studied in 5 human epiphyseal growth plates. 70.5% of all cases stained positive for P-glycoprotein, while 29.5% of the cases were negative. Cases investigated after chemotherapy showed a higher incidence (82.9%) of positive P-glycoprotein immunostaining than cases prior to chemotherapy (64.4%). The Pgp-expression of 34 biopsies was compared with chemotherapy, as determined at the surgical specimen. In these cases, however, no correlation could be established between P-glycoprotein expression of the biopsy and the later response to chemotherapy. 48.4% of the cases with biopsies, initially positive for Pgp, showed a good response in the surgical specimen, while only 27.2% of Pgp-positive biopsies were later classified as non-responders. In the normally growing skeleton, positive immunostaining was detected in the area of mineralization of epiphyseal growth plates. Osteoclasts, hypertrophic chondrocytes, and cuboidal osteoblasts showed Pgp-expression, while there was a lack of Pgp in the majority of osteocytes and chondrocytes in the resting and proliferating zone. These data therefore suggest that P-glycoprotein expression in hgc-OS resembles, at least in part, the phenotype of active bone cells. These results may explain why P-glycoprotein, by using immunohistochemistry, in biopsies of osteosarcomas is insufficient to predict the response to chemotherapy.
Pösl
M
M
Department of Bone Pathology, Institute of Pathology, University of Hamburg, Germany.
Amling
M
M
Grahl
K
K
Hentz
M
M
Ritzel
H
H
Werner
M
M
Winkler
K
K
Delling
G
G
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D005260:Female; D006132:Growth Plate / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis / Q000502:physiology*; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism*; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1