title: [Comparative analysis of the proliferative capacity of cholesteatomas].
abstract: Cholesteatomas of the middle ear are frequently aggressive and produce bone destruction. Stimulation of the surrounding inflammatory tissue and autocrine mechanisms could be responsible for the keratinocytic dysregulation of cholesteatomas, as well as for abnormal proliferation patterns. The proliferative capacity of human cholesteatoma of the middle ear was studied through the kinetics of the epithelial cells of cholesteatomas and external ear canal. The APAAP method was used to study the monoclonal antibody MIB-1, which recognizes an antigen of cells in the division phase. Biopsies taken from the outer ear canal (n = 7) revealed an MIB-1 level (the ratio of MIB-1 positive cells to all cells) of 7.6% +/- 2.2%. Cholesteatoma samples (n = 13) showed an MIB-1 level of 17.4% +/- 8.9%, and heterogeneity of the proliferative areas. Epithelial invaginations into the surrounding stroma were characterized by intense mitotic activity. The results confirmed a statistically significant increase in keratinocytes in the cholesteatomas, with an MIB-1 level 2.3 times higher than that of meatal keratinocytes. PCNA, a nuclear proliferation antigen which expresses the growth phase of cells in normal and tumoral tissue, was determined in 15 biopsies of meatal skin and 7 specimens of cholesteatoma in the phase of infection and 8 non-infection. Although the number of proliferative cells changed depending on the site of the cholesteatorna, the amount of PCNA-positive cells was significantly higher in the cholesteatoma (2.5-15, mean 9.3) than in normal skin (1-2.8, mean 1.5) (p < 0.001). Finally, AgNOR (argyrophyllic nucleolar organizer regions), which express proliferative activity, were determined in 12 specimens of meatal skin and in 19 acquired and 2 congenital cholesteatomas. A mean of 3.71 AgNOR dots were counted in the cholesteatomas and 1.54 dots in meatal skin specimens. The immunohistological study with three different markers expressing cellular proliferative capacity showed hyperproliferation associated with keratinocyte dysregulation in cholesteatoma samples, which could explain the clinically aggressive and destructive behavior of these lesions.
authors.affiliation: Servicio de ORL, Hospital Clínic, Barcelona.
authors.forename: M
authors.initials: M
authors.lastname: Bernal Sprekelsen
authors.forename: J
authors.initials: J
authors.lastname: Ebmeyer
authors.forename: A
authors.initials: A
authors.lastname: Buchbinder
authors.forename: H
authors.initials: H
authors.lastname: Sudhoff
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism; D018424:Cholesteatoma, Middle Ear / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D009697:Nucleolus Organizer Region / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen