Angiogenesis and angiogenic growth factors in middle ear cholesteatoma.
OBJECTIVE
This study aimed to analyze the localization and distribution of vessels and of these angiogenic growth factors: basic fibroblast growth factor (FGF-2), transforming growth factor-alpha (TGF-alpha), transforming growth factor-beta1 (TGF-beta1), and vascular endothelial growth factor (VEGF) in middle ear cholesteatoma in comparison with normal middle ear mucosa and auditory meatal skin.


BACKGROUND
Angiogenesis is particularly important in many normal and pathologic processes, including wound healing and inflammation. Because proliferating tissues require an enhanced blood supply, angiogenesis appears to be a prerequisite for the expansion of cholesteatoma.


METHODS
The expression of FGF-2, TGF-alpha, TGF-beta1, and VEGF was studied by immunohistochemistry. The amount of vessels (collagen type IV staining) was determined by an automatic imaging analyzing system.


RESULTS
The results showed an altered expression and distribution of VEGF, FGF-2, TGF-alpha, and TGF-beta1 in cholesteatoma in relation to middle ear mucosa and auditory meatal skin. The results were consistent with rapidly growing, activated keratinocytes and stromal cells. Vascularization within the perimatrix of cholesteatoma showed a 4.3-fold increase compared with middle ear mucosa and a twofold increase compared with ear canal skin. An increase of 3.2- to 4-fold in the number of vessels was observed. A close relationship was seen between the density of capillaries, degree of inflammation, and expression of the angiogenic factors investigated, and an increased number of microvessels in cholesteatoma tissue.


CONCLUSIONS
Angiogenesis enables and supports the sustained migration of keratinocytes into the middle ear cavity. Therefore, it is a pivotal factor in the destructive behavior of middle ear cholesteatoma.
Sudhoff
H
H
Department of Otorhinolaryngology, Head and Neck Surgery, St. Elisabeth Hospital, University of Bochum, Germany.
Dazert
S
S
Gonzales
A M
AM
Borkowski
G
G
Park
S Y
SY
Baird
A
A
Hildmann
H
H
Ryan
A F
AF
D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D018424:Cholesteatoma, Middle Ear / Q000378:metabolism* / Q000473:pathology*; D046508:Culture Techniques; D016228:Endothelial Growth Factors / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D007150:Immunohistochemistry; D008222:Lymphokines / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D043925:Angiogenesis Inducing Agents; D000911:Antibodies, Monoclonal; D016228:Endothelial Growth Factors; D008222:Lymphokines; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2