No abstract

Proliferation in cholesteatoma epidermal cells is not uncontrolled, as it is in malignant tumors. Our results demonstrate an increase in the rate of proliferation and apoptotic cell death in cholesteatoma epidermis.

With the objective of estimating proliferation ability of epidermis of middle ear cholesteatoma, the difference in proliferating cell nuclear antigen (PCNA) staining between the skin of the bone region of the external ear canal (control skin) and cholesteatoma epidermis and the effects on PCNA staining of subepidermal inflammatory cell infiltration of cholesteatoma were immunohistochemically studied using an antibody against PCNA. Transforming growth factor-alpha (TGF-alpha) is known to promote epidermal proliferation based on autocrine mechanism. But it is not clear that cholesteatoma epidermis is actually in the state of hyperproliferation under the effect of this growth factor. To estimate the effect of TGF-alpha on epidermal proliferation ability, the authors compared the location of PCNA and TGF-alpha in the same specimen. Unlike the control skin, not only epidermal basal cell layer and suprabasal cell layer, but also more superior layers were found to have high levels of PCNA staining in the epidermis of cholesteatoma. However, in the same cholesteatoma epidermal tissue, the PCNA staining was varied and the difference was ascribable to subepidermal cell inflammation. It appeared that the proliferation ability was high in regions where subepidermal inflammatory cell infiltration was severe. These differences in microenvironment are inferred to greatly affect proliferation ability of cholesteatoma epidermis.

The roles of epidermal growth factor (EGF) and epidermal growth factor receptor (EGF-R) in the proliferation and progression of the epithelium of middle ear cholesteatoma were studied. An attempt was made to elucidate the site and degree of localization of the EGF mRNA and EGF-R mRNA in the epithelium of the cholesteatoma by means of the non-radioactive in situ hybridization method. Ten cholesteatoma specimens excised during operations and six normal skin specimens (control) collected from the external ear canal were used in this study. The signal of the EGF mRNA was slightly expressed in part of the basal cells in only one of the six control specimens, while the signal was strongly expressed along the basal cells of the cholesteatoma epithelium in five of the ten specimens. The signal of the EGF-R mRNA was observed along the basal cell layer in five of the six control specimens, while the signal was strongly expressed in all layers of the cholesteatoma epithelium in all ten specimens. The expression was especially marked in the basal cell layer. These findings suggest the possibilities that abnormal expression of the EGF-R mRNA in nearly entire epithelial layers of cholesteatoma is due to overexpression of EGF-R gene, and that there is a mechanism of epithelial basal cell proliferation through an autocrine regulatory system via EGF and EGF-R.

No abstract

The present results indicate that congenital cholesteatoma manifests at an earlier time compared with acquired cholesteatoma, and the results can be thought to support the theory that congenital cholesteatoma originates from vestigial fetal tissue or aberrant tissue. In addition, the finding that telomerase activity was weak in the congenital cholesteatoma tissue suggests the possibility that vestigial fetal tissues and aberrant tissues are naturally eliminated in normal subjects as a result of apoptosis.

No abstract

This study aims at elucidating the role of cytokines in the mechanism of proliferation of cholesteatoma epithelium by investigating the mode of expression of epidermal growth factors, such as TGF-α. The subjects of this study were patients who had undergone operation for middle ear cholesteatoma. Skins of the bone region of the externalear canal (normal skin) of the same patients were used as the negative control. The mode of expression of TGF-α was studied by immunohistochemistry and in situ hybridization. In the immunohistochemical study, there were no conspicuous differences observed between cholesteatoma tissues and normal skin. After in situ hybridization, expression of TGF-α mRNA was mainly observed in the epidermal basal cell layer in the normal skin, while in the cholesteatoma epidermis with severe inflammatory cell infiltration, expression of TFG-α mRNA was observed up to layers superior to the basal cell layer. The expression of TGF-α mRNA is greatly affected by subepithelial connective tissue, strongly suggesting involvement of paracrine regulation in proliferation of cholesteatomaepithelium.