Identification of Proliferating Keratinocytes in Middle Ear Cholesteatoma Using the Monoclonal Antibody Ki-67

Abstract

Cholesteatoma epithelium is characterized by a keratinocyte dysregulation with aggressive growth subsequently destroying the middle ear mucosa. The monoclonal antibody Ki-67 recognizes a nuclear antigen expressed by cells in the G₁, S, and G₂/M phases being used to determine the growing cell fraction in tissue samples. Cryostat sections of skin and cholesteatoma biopsies were examined immunohistochemically for reactivity with Ki-67 using the alkaline phosphatase-anti-alkaline phosphatase method. Nuclear staining was seen in a small number of keratinocytes located in the basal cell layer of normal auditory meatal skin. In contrast, numerous cells of the basal and suprabasal layers in cholesteatoma were found to react with Ki-67. A cytoplasmic staining was also observed in both skin and cholesteatoma. In cholesteatoma, the cytoplasmic staining was stronger. These results clearly show that cholesteatoma epithelium proliferates at a higher rate than normal epidermis, confirming the hyperproliferative behavior of cholesteatoma.

Role of Langerhans cells, Ki-67 protein and apoptosis in acquired cholesteatoma: prospective clinical study

“…3,17 In a study conducted to examine hyperproliferative features of cholesteatoma epithelium, Olszewska et al found greater release of Ki-67 in 18 They demonstrated a high level of proliferative activity in cholesteatoma epithelium, particularly in the basal and suprabasal layers; however, this was unrelated to epithelial thickness. In our study, we did not find any relationship between epithelial thickness and cell proliferation, supporting Olszewska and colleagues' findings.…”

“…Clinically, it is a destructive lesion that may cause hearing loss, vestibular dysfunction, facial paralysis and terminal intracranial complications. [1][2][3] Many classification systems have been proposed for cholesteatoma. At present, the most accepted classification system depends on aetiology, and comprises two main groups: primary (congenital) cholesteatoma and secondary (acquired) cholesteatoma.…”

“…1,4 Recent studies on the pathogenesis of acquired cholesteatoma have focussed on epithelial hyperproliferation, altered differentiation, apoptosis mechanisms and inflammation. 1,[3][4][5][6] In cholesteatoma, inflammation is always present as a response to tissue injury. 4 Langerhans cells have a role as antigen-presenting cells within cutaneous immune defence.…”

Comparative Analysis of the Expression of Involucrin, Filaggrin and Cytokeratin 4, 10, 16 in Cholesteatoma

“…Epidermal homeostasis is maintained by a delicate balance between proliferation and terminal differentiation rate 1). In cholesteatoma, Ki-67, a marker of cell proliferation, positive cells have been significantly observed in the suprabasal layer12) and proliferating cell nuclear antigen positive cells have been detected in the suprabasal and parabasal layer as well as in the basal layer of cholesteatoam epithelium 13). Epidermal growth factor receptor also highly expressed in basal and suprabasal keratinocytes in cholesteatoma 14)…”

Nucleoplasm staining patterns and cell cycle–associated expression of Ki-67 in middle ear cholesteatoma

“…The application of this prototypic antibody was limited to frozen sections, resulting in poor morphology and false-positive results. Undesirable cytoplasmic staining was described in cholesteatoma samples in several reports [13,14]. These falsepositive results could be attributed to poor methodology, inappropriate fixation, or prolonged storage [15].…”