Immunohistochemical Analysis of the Cytokeratin Expression in Middle Ear Cholesteatoma and Related Epithelial Tissues

Abstract

Immunohistochemical investigations were carried out to determine the pattern of cytokeratin (CK) expression in middle ear cholesteatoma and related epithelia. Using monoclonal antibodies specific for CK chains and the indirect immunoperoxidase technique, we examined 10 CK polypeptides for expression. The external stratified squamous epithelium of the tympanic membrane generally expressed CKs 5, 10, and 14. In addition, basal keratinocytes in the annular region of the pars tensa expressed CK 19 (a simple epithelium marker), while suprabasally the hyperproliferative marker CK 16 was expressed. These data reflect the unusual proliferative nature of this region. The unexpected appearance of CK 16 (known to have a limited distribution in healthy epidermis) clearly relates to its expression in the neighboring deep meatus. The medial simple epithelium of the eardrum revealed mucosal CKs 7, 8, 14, 18, and 19. Acquired cholesteatoma lesions, besides CKs 5, 10, and 14, consistently expressed CK 16 in suprabasal layers. These results constitute the first direct molecular evidence for the hyperproliferative nature of the cholesteatoma matrix. Overall, our CK data suggest that aural cholesteatoma lesions and epidermal tissue in this area are related. However, they do not explain the mechanism(s) by which the eardrum or meatal epithelia might invade the middle ear cavity. Congenital cholesteatomas expressed CKs 5, 10, 14, and 16 equally. These CK data do not support the idea of a metaplastic origin from middle ear mucosa; instead, they suggest activation of an ectodermal rest in the middle ear cavity.

Imunoexpressão da citoqueratina 16 e do antígeno nuclear Ki-67 no colesteatoma adquirido da orelha média

“…Porém, ela está sempre presente nas doenças epidérmicas hiperproliferativas 8 , sejam elas benignas (psoríase, verruga vulgar, dermatite de contato, dermatite atópica, dermatomiosite, queratose actínica) ou malignas (carcinoma verrucoso, espinocelular e basocelular). Regiões específicas como o anel timpânico e a região medial e inferior do meato acústico externo, junto ao anel, também expressam esta CK 7,9 . Dentre as substâncias utilizadas como marcadores de proliferação celular, existe o Ki-67, que é um antígeno presente no núcleo das células em fase de multiplicação (fases G 1 tardia, S, G 2 e M do ciclo celular).…”

Marcadores de hiperproliferação na epiderme do meato acústico externo

“…As to study designs, 14 (87.5%) were cross-sectional [1][2][3][4][5][6][7][8][9][10][11][12][13][14] and only two (12.5%) were experimental 15,16 . Among all the papers included in this review, five (31.25%) were published with the only goal of analyzing, by means of immunohistochemistry, the epidermis of the normal external auditory meatus 1,4,5,8,16 .…”

“…Among all the papers included in this review, five (31.25%) were published with the only goal of analyzing, by means of immunohistochemistry, the epidermis of the normal external auditory meatus 1,4,5,8,16 . The other 11 studies (68.75%) were used only as control sample to assess the immunoexpression of cholesteatoma antigens, of the middle or external ear 2,7,8,[10][11][12][13][14][15][16] . Many markers were studied by means of the immunohistochemical methods in the investigations analyzed.…”

“…In the studies which analyzed the EAC epithelium only as control, there was CK 16 expression in the same EAC region, in the suprabasal layers; nonetheless, the au- 1,4,5,8,16 . The cytokeratins were studied in four of the five thors did not report on the place from which the samples were obtained6, except for Broekaert et al 7 who observed CK 16 presence on the fibrocartilaginous annulus, as well as on the juxta-tympanic epithelium (Figure 1). in the EAC epidermis PCNA, and the former observed its expression on the basal layer, extending to the suprabasal layers of the canal epidermis, and the latter only on the basal layer.…”

Algumas considerações sobre colesteatomas adquiridos pediátricos e adultos

“…Lepercque et al 42 described that CK16 does not show on the normal epithelium unless it is in areas under pressure and friction, or on the recover epithelium of hair follicles. According to Broekaert et al 43 , CK16 is expressed in specific regions, such as tympanic ring and medial and inferior regions of the external acoustic canal. Pereira et al 29 stated that the presence of CK16 in the matrix of the cholesteatoma could indicate a hyperproliferative behavior, similar to hyperproliferative epidermal disease.…”