[Proliferative potential of the ear drum in the process of gerbiline cholesteatoma formation]

Mongolian gerbil frequently develop spontaneous cholesteatoma. As we reported previously, in the process of gerbiline cholesteatoma formation, effusions inside the pars flaccida are always found in the ears during the early stage, and epidermal growth factor (EGF) is also localized in the pars flaccida, especially in the mucous layer. In this study, to clarify the process of gerbiline cholesteatoma formation, we studied 22 gerbiline temporal bones by using a monoclonal antibody against bromodeoxyuridine (BrdU). BrdU-labeled cells demonstrate a proliferative potential. We also used a carbon dye method to label the micro-vase in 14 gerbiline temporal bones. Cells showing BrdU uptake were more abundant, as demonstrated immunohistochemically, in the pars flaccida of ears with early cholesteatomas than in the pars flaccida of normal ears (p < 0.01). The pars flaccida of ears with early cholesteatomas showed hypertrophy of both epithelial layers, and hyperkeratosis of the epidermal layer. BrdU-labeled cells in the pars flaccida were more localized in the mucous layers than in the epidermal layers. In contrast, in ears with cholesteatomas, BrdU-labeled cells were less abudant than in ears with early cholesteatomas. In addition, BrdU-labeled cells in the pars tensa and external auditory epidermal layers were not increased in ears with any stage of cholesteatoma formation. We used a carbon dye method to detect the micro-vasa in the intermediate layer of the ear drum. Carbon-dye-labeled vasa were more numerous in the pars flaccida with early cholesteatomas than in the pars flaccida of normal ears or ears with cholesteatomas. It is highly suspected that angiogenesis was stimulated in the pars flaccida with early cholesteatomas, because stimulation of angiogenesis by EGF has been reported. The above findings suggest that the mucous layer of the pars flaccida has the greatest proliferative potential in the process of cholesteatoma formation. Angiogenesis in the pars flaccida appears to be a reaction to proliferative changes in the mucous and epidermal layers. These changes are probably stimulated by effusion inside the pars flaccida.