Possible autocrine growth stimulation of cholesteatoma epithelium by transforming growth factor alpha.

ABSTRACT

INTRODUCTION: Transforming growth factor alpha (TGF-alpha) is known to be produced by normal human keratinocytes and to stimulate their proliferation. The squamous epithelium of middle ear cholesteatoma is believed to exhibit hyperproliferative characteristics. This study was undertaken to determine if growth factors can be identified in cholesteatoma. MATERIALS AND METHODS: Cholesteatoma samples (n = 6) and retroauricular skin (n = 9) were obtained during surgery. Monoclonal antibody against epidermal growth factor (EGF) and TGF-alpha were evaluated in these specimens using immunohistochemical techniques. RESULTS: Epidermal growth factor receptor (EGF-R) was highly expressed in the basal layer of the epidermis, hair follicles, eccrine sweat glands, and the capillary system of normal skin. In the majority of cholesteatoma samples, expression of EGF-R was not confined to the basal layer but persisted in suprabasal cells of the stratum spinosum and stratum granulosum. In two cases, heterogenous standing was found in different parts of the same cryosection. Staining for TGF-alpha was consistently stronger in cholesteatoma than in normal skin, and encompassed all epithelial cell layers. Immune cells infiltrating the stroma of cholesteatoma stained positively for TGF-alpha. CONCLUSION: These data are consistent with autocrine stimulation of the squamous epithelium of cholesteatoma by TGF-alpha contributing to its unrestrained growth in the middle ear cavity.