Down-regulation of p27(Kip1) expression is correlated with increased cell proliferation but not expression of p21(waf1) and p53, and human papillomavirus infection in benign and malignant tumours of sinonasal regions

Aims: Although p27(Kip1)(p27) is a cyclin-dependent kinase inhibitor and a contribution to tumorigenesis has been hypothesized, the possible role in t umours arising in the nasal and paranasal sinus regions is still unknown. Methods and results: Seventy-six sinonasal tumours, including 28 inverted p apillomas (IPs) and 48 squamous cell carcinomas (SCCs), were immunohistoche mically investigated, along with 46 exophytic papillomas (EPs) of upper res piratory tract and 34 samples of normal paranasal sinus epithelium. The res ults were also compared with expression of p21(WAF1) (p21) and p53, cell pr oliferation assessed in terms of Ki67 labelling indices (LIs), and human pa pillomavirus (HPV) infection. The average p27 scores decreased from normal through to malignant lesions, while Ki67 LI scores showed a stepwise increa se, the inverse correlation between scores for all categories being signifi cant (r = - 0.639, P < 0.0001). In the SCCs, p27 expression was significant ly higher in keratinizing than nonkeratinizing type tumours (P<0.05), while there was no association with p21 and p53 expression. Although HPV DNAs fo r type 16 and 18 were detected in two (7.4%) of 27 EPs, six (35.8%) of 28 I Ps, and nine (28.1%) of 32 SCCs, no relation with p27 scores was evident. Conclusion: Loss of p27 expression correlates with increased cell prolifera tion in sinonasal tumours. Moreover, the expression appears to be associate d with keratinization in SCCs of the paranasal sinus. These findings indica te that p27 expression may be a useful marker for the dysregulation of cell kinetics in these tumours.