Congenital
cholesteatomas are epithelial lesions that present as an epithelial pearl behind an intact eardrum. Congenital and acquired
cholesteatomas progress quite differently from each other and progress patterns can provide clues about the unique origin and pathogenesis of the abnormality. However, the exact pathogenic mechanisms by which
cholesteatomas develop remain unknown. In this study, key
proteins that directly affect
cholesteatoma pathogenesis are investigated with proteomics and immunohistochemistry.
Congenital cholesteatoma matrices and retroauricular skin were harvested during surgery in 4 patients diagnosed with a
congenital cholesteatoma. Tissue was also harvested from the retraction pocket in an additional 2 patients during middle ear surgery. We performed 2-dimensional (2D) electrophoresis to detect and analyze spots that are expressed only in
congenital cholesteatoma and matrix-assisted
laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/MS) to separate
proteins by molecular weight.
Protein expression was confirmed by immunohistochemical staining. The image analysis of 2D electrophoresis showed that 4
congenital cholesteatoma samples had very similar
protein expression patterns and that 127 spots were exclusively expressed in congenital
cholesteatomas. Of these 127 spots, 10 major spots revealed the presence of
titin, forkhead transcription activator homolog (FKH 5-3),
plectin 1,
keratin 10, and leucine zipper
protein 5 by MALDI-TOF/MS analysis. Immunohistochemical staining showed that FKH 5-3 and
titin were expressed in
congenital cholesteatoma matrices, but not in acquired
cholesteatomas. Our study shows that
protein expression patterns are completely different in congenital
cholesteatomas, acquired
cholesteatomas, and skin. Moreover, non-epithelial
proteins, including FKH 5-3 and
titin, were unexpectedly expressed in
congenital cholesteatoma tissue. Our data indicates that
congenital cholesteatoma origins may differ from those of acquired
cholesteatomas, which originate from retraction pocket epithelia.