EGFR expression in acquired middle ear cholesteatoma in children and adults

Abstract

Middle ear cholesteatomas are characterized by the presence of keratinized stratified squamous epithelium inside this cavity. It is considered to be more aggressive in childhood. In normal skin, the epidermal growth factor receptor (EGFR) is expressed in the cytoplasmic membrane of epithelial cells of the basal layer. In contrast, its expression in middle ear cholesteatoma extends to suprabasal layers. The objective of this study is to detect the presence of EGFR in cases of acquired cholesteatoma of the middle ear and correlate the expression of this receptor with patients' ages. In this cross-sectional study, cholesteatoma samples were collected from 50 patients (35 adults and 15 children) who underwent otological surgery, throughout 1 year of study. These samples were subjected to histological and immunohistochemical assays. Results were submitted to statistical analyses and main findings were: EGFR was present in the parabasal layers in 27 cases and EGFR expression was extended to all layers of the matrix in 17 cases. There were no statistically significant differences in what concerns age-related variances in EGFR expression. The intensity and location of EGFR expression in acquired cholesteatoma of the middle ear confirm the hyperproliferative capacity of keratinocytes.

Biology of cholesteatoma: Special considerations in pediatric patients

“…As an example, increases in signal transduction from EGFR results in a variety of cellular events including the induction of hyperplasia, growth, proliferative cytokeratin expression, and tumor invasiveness. Not surprisingly, in cholesteatoma EGFR expression is not limited to the basal layer, as it is in normal squamous epithelia, but is also increased in the suprabasal strata [15]. In keratinocytes, the EGFR pathway activates map kinases and intracellular transcription factors such as AP-1 that will induce a proliferative phenotype.…”

Acquired cholesteatoma: summary of the cascade of molecular events

“…Cholesteatoma is a growth disorder, and the epidermal growth factor receptor and keratinocyte growth factor receptor are up-regulated in cholesteatoma pathogenesis, 20 – 23 as is the ligand for the epidermal growth factor receptor, namely amphiregulin 24 . In addition, increased p63 expression and keratinocyte markers demonstrate uncoordinated hyperproliferation, migration and invasion properties 25 – 28 .…”

MicroRNA let-7a suppresses the growth and invasion of cholesteatoma keratinocytes

“…A previous study demonstrated that keratinocyte proliferation and migration is mediated by growth factors and their receptors (1). An upregulation of epidermal growth factor (EGF) and its receptor (EGFR), and of keratinocyte growth factor (KGF) and its receptor (KGFR) have previously been reported in cholesteatomas (3)(4)(5)(6). Further studies have suggested that an upregulation of these growth factors and their receptors induces cell proliferation of keratinocytes in cholesteatomas (7)(8)(9).…”