Relation of the ErbB2 gene in pathogenesis of Hirschsprung disease

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 12671210
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: NIIGATA UNIVERSITY
• Principal Investigator: YAGI Minoru NIIGATA UNIVERSITY Graduate School of Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (10251802)
• Co-Investigator(Kenkyū-buntansha): KANADA Satoshi Medical Hospital Assistant, 医学部附属病院, 助手 (90313535) ; IWAFUCHI Makoto Labour Welfare Corporation Tsubame Rosai Hospital, Director Administration Department, 院長 (00018326)
• Project Period (FY): 2000 – 2002
• Keywords: Hirshsprung disease / Pathogenesis / ErbB2 gene

Research Abstract

Recently some studies have reported that some genetic alterations are related to the causation of Hirschsprung disease. Professor Lee KF in Salk laboratory in USA advocated that ErbB-2 gene knocked-out mice exhibit ventricle cordis malformation associated with decrease of ganglion cells. We hypothesized that this genetic mutation or deletion are related to the occurrence of this disease. In this study 19 cases of this disease experienced between 1991 to 2002 in our hospital were selected. We investigated the overexpression of this ErbB-2 protein, and analyzed the genetic abnormalities used by RT-PCR method and direct sequence. HE specimens of each case were evaluated separated by normo-ganglionic areas and aganglionic areas. Immunohistochemically, NSE (neuron specific enolase) reactivity confirmed us the existence of normal facial ganglion cells and we analyzed the immunoreactivity of ErbB-2. Usually overexpression of this gene is reported in breast cancer, lung cancer and Wilms tumor. Immunoreactivity of ErbB-2 were detected in ganglion cells of 7 cases (36.8%). Otherwise the molecular analysis about the genetic abnormalities are not accomplished because the time was necessary to obtain the technique of immunohistochemical analysis. We have a plan to evaluate the abnormalities using peripheral blood of these patients and to examine the genetic site discussed in osteosarcoma or Ewing sarcoma. We speculate that some germline mutations are associated because the overexpression was observed even in the normo-facial ganglion cells in this disease. We are trying to continue this research using molecular technique.