PAPS papersHedgehog signaling pathway in neuroblastoma differentiation
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Clinical data of patients and biological data of NB samples
Patients were diagnosed with NB between April 1988 and March 2008. Eighty-two NB samples and 10 ganglioneuroblastoma samples were obtained. The tumor was staged according to the International Neuroblastoma Staging System (INSS). All of the parents of the patients provided informed consent for tumor preservation and the biological analysis before surgery. This study was performed according to ethical guidelines for the clinical studies by Ministry of Health, Labour, and Welfare of Japan in July
Association of expression of Shh, GLI1, and Ptch1 proteins and the status of MYCN gene
The Shh and Ptch1 staining was observed in the cell membrane strongly, and GLI1 was localized in the cytoplasm in neuroblasts with ganglionic differentiation in GNB samples (Fig. 1A). The Shh, GLI1, and Ptch1 staining intensity of GNBs was higher than that of NBs, and most Schwann cells were negative for Shh, GLI1, and Ptch1 (Fig. 1A, B).
The result of immunohistochemistry of 92 samples is shown in Table 1. Sixty-seven of 92 samples (73%) were positive for Shh, 62 (67%) for GLI1, and 73 (79%)
Discussion
The current study showed that Hh signaling pathway–associated proteins such as Shh, GLI1, and Ptch1 were expressed in most NB cases, especially cases without MYCN amplification. Moreover, a number of positive cases show “++”, whereas “+” cases are rare. As a result, most of the positive cases tended to be easy to distinguish as positive cases. The percentage of GLI1-positive cells in early-stage samples was higher than that with advanced stage. The 5-year OS rate of GLI1-positive cases without
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