MECHANISMS OF AUTOCRINE GROWTH IN MIDDLE- EAR CHOLESTEATOMA

Transforming growth factor alpha (TGFalpha) and interleukin 1alpha (IL -1alpha) are known to be produced by normal human keratinocytes stimul ating their proliferation. The distribution and expression of TGFalpha and IL-1alpha were examined in specimens of middle ear cholesteatoma by means of immunohistochemical methods using a monoclonal antibody ag ainst TGFalpha and a polyclonal one against IL-1alpha. Normal retroaur icular skin was stained for comparison. Staining for TGFalpha was cons istently stronger in cholesteatoma epithelium than in normal epidermis , and encompassed all epithelial cell layers. Immune cells occurring i n the stroma of cholesteatoma also reacted positively for TGFalpha. Th e intensity of staining for IL-1alpha was markedly stronger in cholest eatoma tissue than in normal epidermis. All cellular layers of the squ amous epithelium of cholesteatoma stained strongly and uniformly for I L-1alpha, whereas the keratin layer was negative for IL-1alpha. In the connective tissue beneath the cholesteatoma epithelium intensely posi tive cells were scattered between negative stromal cells. These data a re consistent with autocrine stimulation of the squamous epithelium of cholesteatoma by TGFalpha and IL-1alpha as well as with a paracrine s timulation by immune cells. Both factors contribute to the unrestraine d growth of cholesteatoma in the middle ear cavity.