Keratinocyte differentiation in acquired cholesteatoma and perforated tympanic membranes
P. P. Vennix, W. Kuijpers, T. A. Peters, E. L. Tonnaer and F. C. Ramaekers
Department of Otorhinolaryngology, University of Leiden, The Netherlands.
OBJECTIVE: To evaluate the type of differentiation of keratinocytes of
acquired cholesteatoma and its significance for cholesteatoma invasiveness.
DESIGN: Forty acquired cholesteatomas and 10 tympanic membranes with
persisting perforations were snap frozen and processed for
immunohistochemical studies. Cytokeratin antibodies that represented all
subgroups and antibodies that were directed against collagen components of
the basal lamina were applied. Expression of these constituents was scored
by using light microscopy. RESULTS: The phenotype of the matrix was
generally characterized by an extension of expression of basal cell
cytokeratin 14 and hyperproliferation-associated cytokeratins 6, 16, and 17
into the suprabasal cell layers, while the expression of keratinization
marker cytokeratin 10 was down-regulated. These features varied greatly at
different sites of the matrix and were most marked at the advancing front
of the cholesteatoma. A comparable expression pattern, but less pronounced,
was observed at the epidermal front of the mucocutaneous junction of the
tympanic membrane perforations. This phenomenon was invariably associated
with a mononuclear cell infiltrate in the dermis at both junctions. The
basal lamina was always intact. CONCLUSIONS: Acquired cholesteatomas show
hyperproliferative features. There is a striking similarity between the
pronounced expression of this phenotype and the associated inflammation at
the mucocutaneous junctions of cholesteatomas and tympanic membrane
perforations and those that are observed after epidermal injury. This
indicates that epidermis and middle ear epithelium do not form stable
junctions and the front can be considered to be a persisting epidermal
defect. This involves the permanent presence of "activated keratinocytes"
in the junction area that will lead to proliferation and migration, when
additional triggers are present.
