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Hiromi Kojima, MD; Akio Matsuhisa, PhD; Masanori Shiwa, MD; Yosuke Kamide, MD; Mariko Nakamura, MD; Tsuneya Ohno, MD; Hiroshi Moriyama, MD

Arch Otolaryngol Head Neck Surg. 1996;122(2):157-160.

Abstract
Objective
To understand the interaction between cholesteatoma epithelium and subepithelial connective tissue as a paracrine regulation by keratinocyte growth factor.

Design
Preparation of a specific DNA probe from human fetal fibroblast and detection of localization of keratinocyte growth factor messenger RNA in subepithelial granulation tissue of middle-ear cholesteatoma by a nonradioactive in situ hybridization method.

Participants
The cholesteatoma specimens were excised from 12 patients during surgery. Normal skin specimens collected from the external ear canal of six patients were used as controls.

Results
Signals specific for keratinocyte growth factor messenger RNA were not expressed in the normal skin of the external ear canal, but were observed in fibroblasts of subepithelial connective tissue of cholesteatoma specimens. Signals were observed only in specimens collected from patients whose subepithelial connective tissue was thick and proliferated and whose inflammation was strong.

Conclusions
A paracrine regulation mechanism involving keratinocyte growth factor may exist for proliferation of epithelium of cholesteatoma. The subepithelial connective tissue of cholesteatoma may play an important role in the proliferation and development of the cholesteatoma, especially under inflammatory conditions.

(Arch Otolaryngol Head Neck Surg. 1996;122:157-160)

Author Affiliations
From the Departments of Otorhinolaryngology (Drs Kojima, Shiwa, Kamide, and Moriyama) and Microbiology (Drs Nakamura and Ohno), Jikei University School of Medicine, Tokyo, Japan; and the Department of Biological Science Research, Research and Development Center, Fuso Pharmaceutical Industries Ltd, Osaka, Japan (Dr Matsuhisa).

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