P-glycoprotein expression in cartilaginous tumors

Background and Objectives: Malignant cartilage tumors demonstrate chemotherapeutic resistance through undetermined mechanisms. Pglycoprotein is the protein product of the multiple drug resistance gene I (MDR-I) and confers multidrug chemotherapeutic resistance in a variety of malignancies. Methods: MDR-I expression was examined in 55 benign and malignant cartilage tumor specimens by immunohistochemistry using C219, C494, and JSB-1 antibodies, and by in situ hybridization with an MDR-I specific oligonucleotide cDNA probe. Results: Constitutive expression of P- glycoprotein was observed in all benign and malignant cartilage tumor specimens with a similar pattern of immunohistochemical staining present with all three antibodies. In benign tumors and low grade chondrosarcomas, the staining pattern was weak to intermediate and localized to clusters of cells. However, higher grade tumors (Grade II and III) expressed P-glycoprotein in a higher percentage of cells and with more intense staining. P-glycoprotein expression was absent in normal human articular cartilage, but was focally present in costal and growth plate cartilage. The immunohistochemistry results were confirmed by in situ hybridization in 10 cases. Conclusions: P- glycoprotein is expressed constitutively in cartilaginous tumors, with greatest expression in high grade malignancies. The findings may account for the resistance of cartilage tumors to chemotherapeutic agents.