Expression of hypoxia inducible factor 1 alpha and Von Hippel Lindau protein in human middle ear cholesteatoma.
OBJECTIVE
To evaluate the role of hypoxia in cholesteatoma progression.


METHODS
Immunohistochemical analysis of paraffin-embedded human specimens.


METHODS
Thirteen middle ear cholesteatomas and 10 samples of normal human external ear canal skin were stained immunohistochemically for the presence of hypoxia inducible factor 1 alpha (HIF 1 alpha) and Von Hippel Lindau protein. Specimens were then analyzed semiquantitatively.


RESULTS
Staining for both antibodies could be detected in all cholesteatomas (perimatrix and matrix), as well as in the samples of normal human ear canal skin. Cholesteatoma specimens showed statistically significant increased staining when compared with normal human skin and mucosa. The age of patients and relapse surgery affected immunohistochemical staining of HIF 1 alpha and Von Hippel Lindau protein.


CONCLUSIONS
Elevated staining intensities for HIF 1 alpha and Von Hippel Lindau protein in cholesteatoma tissue indicated that cholesteatoma may be hypoxic. In addition, our data indicated that relapse cholesteatomas yield a higher degree of hypoxia than ears without surgery.
Adunka
Oliver
O
Department of Otorhinolaryngology, J.W. Goethe University Clinic Frankfurt am Main, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. adunka@em.uni-frankfurt.de
Gstoettner
Wolfgang
W
Knecht
Rainald
R
Kierner
Antonius C
AC
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D018424:Cholesteatoma, Middle Ear / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004424:Ear Canal; D005260:Female; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D008025:Ligases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human