Division of Pediatric Surgery, Department of Surgery, Osaka University Graduate school of Medicine, Osaka 565-0871, Japan.
J Pediatr Surg. 2010 Feb;45(2):387-92. doi: 10.1016/j.jpedsurg.2009.10.081.
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.
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.
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.
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.
hedgehog（Hh）信号的激活与多种癌症的进展有关。然而，Hh 信号与儿科恶性肿瘤的发生之间的相关性尚未得到很好的记录。本研究旨在检查 Hh 信号通路在各种儿科肿瘤中的表达，以阐明 Hh 信号在儿科恶性肿瘤中的作用。
从 68 名患有儿科恶性肿瘤（神经母细胞瘤 25 例；横纹肌肉瘤 18 例；肝肿瘤 12 例；肾肿瘤 13 例）的患者中获得手术标本。使用免疫组织化学染色评估 sonic hedgehog（Shh）、其受体 Patched（Ptch）和下游转录因子 Gli1 的表达。
在神经母细胞瘤中，Shh、Ptch 和 Gli1 的阳性表达率分别为 96%、100%和 68%；在横纹肌肉瘤中，分别为 78%、100%和 78%；在 Wilms 瘤中，分别为 71%、100%和 43%；在肝母细胞瘤中，分别为 100%、100%和 73%。分化型神经母细胞瘤细胞的 Gli1 表达比未成熟神经母细胞瘤细胞更强烈。在横纹肌肉瘤中，Gli1 的表达在肺泡型中高于胚胎型。
这些发现表明，Shh-Ptch1-Gli1 信号通路在大多数儿科恶性肿瘤中经常被激活。因此，Hh 信号通路可能在儿科恶性肿瘤的分化和恶性潜能中发挥重要作用。
