Detection and significance of glutathione-S-transferase pi in osteogenic tumors of dogs

In this study we describe a relationship between the percentage of tumor cells staining positive for GST pi and the response to cisplatin treatment in dogs with appendicular osteosarcoma. Clinical resistance to platinum compounds has been attributed to tumor cell resistance to the drug. An overexpression of glutathione-S-transferase pi has been implicated in the resistance of tumor cells in vitro to cisplatin. In this study, the relative concentration of GST pi was quantified immunohistochemically in formalin-fixed, paraffin-embedded histologic specimens obtained from dogs with appendicular osteosarcoma prior to cisplatin treatment. The percentage of tumor cells staining positive for GST pi was compared with patient response (remission and survival times) following treatment. Those osteosarcoma-bearing dogs having a low pre-treatment tumor expression of GST pi (<50%; n=13) had a significantly longer (p <0.01) median remission and survival time (24.0 and 33.7 weeks, respectively) than those dogs with a high pre-treatment tumor expression of GST pi (>50%; n=8; median remission and survival times 14.2 and 24.0 weeks, respectively). The relative staining of GST pi in primary canine bone tumors has therapeutic importance and warrants further evaluation as a therapeutic model for human osteosarcoma.