Role of downstream signal transduction molecules of congenital middle ear cholesteatoma according to its site of origin

OBJECTIVES: The pathogenesis of congenital cholesteatoma in the middle ear including its hyperproliferative characteristics is still unknown. If the clinical characteristics of congenital middle ear cholesteatoma are different according to the location, we can imagine that its pathogenesis may be also different. The proliferation and differentiation of cells in specialized tissues and the expression of their properties are under the control of a large number of regulatory processes and complex interactions called signal transduction. The signal transduction pathway may be initiated by the external signals such as growth factors which bind to their receptors and activate tyrosine kinases in the plasma membrane. This study was aim to anayze clinical characteristics according to the site of origin and to investigate the distribution of EGFR, PDGFR, PLC-γ1, and PI3 kinase in human congenital middle ear cholesteatoma. This study may facilitate better understanding of its pathogenesis. MATERIALS AND METHODS: We reviewd 75 cases of congenital middle ear cholesteatoma to determine its pathogenesis by analysing the findings of eardrum, operation and temporal bone computed tomograpy. By RT-PCR and immunohistochemical techniques, we investigated the reaction patterns of antibodies to PLC-γ1, EGFR, PDGFR-α, PDGFR-β, and PI3 kinase as the proliferation and differentiation markers in 10 human congenital middle ear cholesteatoma specimens. For the control, same study was performed with retroauricular skin. RESULTS: The congenital middle ear cholesteatoma originated from posterosuperior quadrant of mesotympanum showed higher degree of hearing loss and more frequent unusaul presentation, and dectected at an older age than cholesteatoma originated from anterosuperior quadrant. In RT-PCR, EGFR and PLC-γ1 were detected in cholesteatoma epitheliums, while PDGFR-α and PI3K were not detected. Only PDGFR-β was detected in retroauricular skins. In immunohistochemical staining, intensity of PDGFR-α was not expressed in cholesteatoma epitheliums and retroauricular skins. Very weak expression of PI3K was detected in some cholesteatoma epitheliums. EGFR protein was detectable in both basal cell and the suprabasal cell layers of cholesteatoma epitheliums, while it was detectable only in the basal cell layer of retroauricular skins. Expression of PDGFR-β was detected in some cholesteatoma epitheliums and in retroauricular skins. Expression of PLC-γ1 at the suprabasal cell layer and basal cell layer were more intense in cholesteatoma epitheliums than that in retroauricular skins. CONCLUSION: The pathogenesis of congenital cholesteatoma may be different according to its site of origin. However, the role of downstream signal transduction pathway of congenital middle ear cholesteatoma through EGFR and PLC-γ1 seemed to be same between ASQ origin and PSQ orign.

Author dc:creator

• 조, 민정

Contributors dc:contributor

• 박, 기현
• 대학원 의학과
• 103777

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000000893
000000000893

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1519