Involvement of keratinocyte growth factor (KGF) and its receptor (KGFR) in the enhancement of proliferative activity of epithelial cells in middle ear cholesteatoma

The middle car cholesteatoma is histologically characterized by enhanced proliferation of epithelial cells and granular tissue formation, though the molecular mechanism underlying the pathogenesis is largely unknown. KGF is known to be a mesenchymal cell-derived paracrine growth factor that specifically stimulates epithelial cell growth. Thus, it can be assumed that KGF plays essential roles in the pathogenesis of cholesteatoma. We examined the expression of KGF, KGFR and Ki-67 in the sections of cholesteatoma specimens (n = 49) by immunohistochemistry and analyzed the correlation between Ki-67 labeling index (LI) and the state of KGF and/or KGFR expression. KGF was detected in the stromal cells in 73 % of 49 cases, and KGFR was found in the epithelial cells of basal and spinous layers in 73 % of same cases. Moreover, 32 out of 49 cases were positive to both KGF and KGFR, in which Ki-67 LI was significantly higher than other cases. These results indicated that co-expression of KGF and KGFR may be involved in the pathogenesis of cholesteatoma by accelerating the proliferation of epithelial cells.