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Sarcoma
Volume 2014 (2014), Article ID 261804, 9 pages
http://dx.doi.org/10.1155/2014/261804
Research Article

Aberrant Hedgehog Signaling and Clinical Outcome in Osteosarcoma

1Department of Molecular Genetics, University of Toronto, ON, Canada M5S 1A8
2Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, Canada M5G 1X5
3University Musculoskeletal Oncology Unit, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5
4Department of Surgery, University of Toronto, ON, Canada M5G 1L5

Received 28 October 2013; Revised 5 February 2014; Accepted 17 February 2014; Published 30 March 2014

Academic Editor: Akira Kawai

Copyright © 2014 Winnie W. Lo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.