Korean J Otolaryngol-Head Neck Surg.  2004 Jul;47(7):617-625.

Expression of Angiogenic Growth Factor in Middle Ear Cholesteatoma

• Baek MJ
• Bang EK
• Hwang MS
• Han TH
• Park SK
• Eom JW
• Goh EK

Abstract

BACKGROUND AND OBJECTIVES
Angiogenesis is important both in normal and pathologic processes, including wound healing and inflammation. Because proliferating tissues require an enhanced blood supply, angiogenesis appears to be a prerequisite for expansion of cholesteatoma. This study was aimed to investigate mRNA and protein expression of angiogenic growth factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-alpha (TGF-alpha) and platelet derived-endothelial cell growth factor (PD-ECGF) in middle ear cholesteatoma. SUBJECTS AND METHOD: Cholesteatoma tissues and retroauricular skins were obtained from 12 patients during operation. The mRNA expression was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), and the degree of expression was measured by comparing density ratio of beta-actin by NIH imaging analysis system. The protein expression was evaluated by immunohistochemistry, and the degrees of expression in epithelial, endothelial, inflammatory cells of cholesteatoma and retroauricular skin were judged by two pathologists and then converted on a 5-grade rating scale according to intensity of expression. RESULTS: The expression rate of mRNA in cholesteatoma and retroauricular skin was 67.7 and 33.3% in VEGF, 75.0 and 50.0% in bFGF, 53.8 and 8.3% in TGF-alpha, 67.7 and 75% in PD-ECGF. There was statistically significant difference only in TGF-alpha (p<0.05). The degrees of VEGF, bFGF, and TGF-alpha mRNA expression were about 2.6, 2.1 and 5.2 times significantly higher than retroauricular skin (p<0.05). And the degree of mRNA of PD-ECGF expression was about 1.4 times higher than retroauricular skin, although there was no statistical significance (p>0.05). The degrees of VEGF, bFGF and PD-ECGF protein expression in cholesteatoma tissue were more intense at the inflammatory (p<0.05), endothelial (p<0.05) and epithelial cell (p>0.05) than in retroauricular skin. And the degree of TGF-alpha protein expression in cholesteatoma tissue was more intense at all three cells (p<0.05) than in the retroauricular skin. CONCLUSION: These results suggest that angiogenesis processes in cholesteatoma perimatrix and the expression of angiogenic growth factors are upregulated by mRNA. Further studies for evaluating the factors that can affect the expression of mRNA and also for disclosing the roles and control mechanisms of these factors in cholesteatoma angiogenesis must be followed.

Keyword

Cholesteatoma middle ear; Angiogenesis factor

MeSH Terms

Actins
Angiogenesis Inducing Agents
Blood Platelets
Cholesteatoma
Cholesteatoma, Middle Ear*
Ear, Middle*
Epithelial Cells
Fibroblast Growth Factor 2
Humans
Immunohistochemistry
Inflammation
Intercellular Signaling Peptides and Proteins
Pathologic Processes
RNA, Messenger
Skin
Thymidine Phosphorylase
Transforming Growth Factor alpha
Vascular Endothelial Growth Factor A
Wound Healing
Actins
Angiogenesis Inducing Agents
Fibroblast Growth Factor 2
Intercellular Signaling Peptides and Proteins
RNA, Messenger
Thymidine Phosphorylase
Transforming Growth Factor alpha
Vascular Endothelial Growth Factor A