Increased expression of the hedgehog signaling pathway in pediatric solid malignancies.

PURPOSE: The activation of the hedgehog (Hh) signaling is involved in the progression of various cancers. However, the correlation between the Hh signaling and tumorigenesis of pediatric malignancies has not been well documented. The present study was undertaken to examine the expression of the Hh signaling pathway in various pediatric tumors to elucidate the role of Hh signaling in pediatric malignancies.

METHODS: Surgical specimens were obtained from 68 patients with pediatric malignancies (neuroblastoma, 25; rhabdomyosarcoma, 18; hepatic tumor, 12; and renal tumor, 13). The expression of sonic hedgehog (Shh), its receptor Patched (Ptch), and downstream transcription factor Gli1 was evaluated using immunohistochemical staining.

RESULTS: In neuroblastoma, 96%, 100%, and 68%; in rhabdomyosarcoma, 78%, 100%, and 78%; in Wilms' tumor, 71%, 100%, and 43%; and in hepatoblastoma, 100%, 100%, and 73% of the specimens stained positive for Shh, Ptch, and Gli1, respectively. Differentiated neuroblastoma cells showed more intense Gli1 expression than in immature neuroblastoma cells. In rhabdomyosarcoma, the expression of Gli1 was higher in alveolar type than in embryonal type.

CONCLUSIONS: These findings suggest that the Shh-Ptch1-Gli1 signaling pathways are frequently activated in most pediatric malignant tumors. The Hh signaling pathway may therefore play an important role in the differentiation and malignant potential of pediatric malignancies.