Aberrant hedgehog signaling and clinical outcome in osteosarcoma

Winnie W Lo; Dushanthi Pinnaduwage; Nalan Gokgoz; Jay S Wunder; Irene L Andrulis

doi:10.1155/2014/261804

Aberrant hedgehog signaling and clinical outcome in osteosarcoma

Sarcoma. 2014:2014:261804. doi: 10.1155/2014/261804. Epub 2014 Mar 30.

Authors

Winnie W Lo¹, Dushanthi Pinnaduwage², Nalan Gokgoz², Jay S Wunder³, Irene L Andrulis¹

Affiliations

¹ Department of Molecular Genetics, University of Toronto, ON, Canada M5S 1A8 ; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, Canada M5G 1X5.
² Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, Canada M5G 1X5.
³ Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, Canada M5G 1X5 ; University Musculoskeletal Oncology Unit, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5 ; Department of Surgery, University of Toronto, ON, Canada M5G 1L5.

Abstract

Despite the importance of Hedgehog signaling in bone development, the relationship between Hedgehog pathway expression and osteosarcoma clinical characteristics and outcome has not been investigated. In this study of 43 high-grade human osteosarcoma samples, we detected high expression levels of the Hedgehog ligand gene, IHH, and target genes, PTCH1 and GLI1, in most samples. Further analysis in tumors of patients with localized disease at diagnosis identified coexpression of IHH and PTCH1 exclusively in large tumors. Higher levels of IHH were observed more frequently in males and patients with higher levels of GLI1 were more responsive to chemotherapy. Subgroup analysis by tumor size and IHH expression indicated that the well-known association between survival and tumor size was further refined when IHH levels were taken into consideration.