Cell proliferation and p27Kip1 expression in endophytic schneiderian papillomas

Objective: To clarify epithelial cell proliferation and p27(Kip1) expression along the stepwise histological changes from endophytic schneiderian papillomas to associated carcinomas. Study Design: Retrospective investigation involved surgical specimens from 58 patients. Methods: Immunohistochemical assessment involved the nuclear Ki67 antigen expressed in proliferating cells. Further, the cyclin-dependent kinase (cdk) inhibitor p27(Kip1) was assessed. Binding of p27(Kip1) to the cyclin E-cdk2 complex inhibits this kinase, which results in cell cycle arrest. The expression rates of both proteins were compared between non-papillomatous nasal mucosa, endophytic schneiderian papillomas, carcinoma in situ and invasive squamous cell carcinomas. Statistics involved the Wilcoxon and Mann-Whitney u tests. Significance was set at P <.05. Results: Comparable cell proliferation rates were observed between non-papillomatous nasal mucosa and cylindrical cell papillomas. Significant increases in cell proliferation were found along the stepwise series of histological changes involving non-papillomatous nasal mucosa, columnar epithelium in inverted papillomas, transitional and squamous metaplasia in inverted papillomas, and dysplastic inverted papillomas (P <.05, respectively). A tendency toward increased cell proliferation in carcinoma in situ compared with dysplastic inverted papillomas was present; however, this was not statistically significant. The expression rates of p27(Kip1) were comparable between non-papillomatous nasal mucosa and all histological subtypes within non-dysplastic endophytic schneiderian papillomas. Significantly reduced p27(Kip1) expression was found in surface cells in dysplastic compared with non-dysplastic inverted papillomas, as well as in the total number of cells in carcinoma in situ compared with dysplastic inverted papillomas (P <.05, respectively). Conclusions: Inverted papillomas but not cylindrical cell papillomas show increased cell proliferation compared with non-papillomatous nasal mucosa. Stepwise increases in cell proliferation accompany the consecutive histological changes within inverted papillomas. Among them, increased cell proliferation along with the development of dysplasia and carcinoma in situ is associated with reduced p27(Kip1) expression.