Low Expression of P27(Kip1) in Advanced Mucoepidermoid Carcinomas of Head and Neck

Background: p27(Kip1), a cyclin-dependent kinase inhibitor, negatively regulates the G1 phase progression of the cell cycle by binding to the cyclin E/cyclin-dependent kinase 2 complex. This study was done to investigate the expression of p27(Kip1) in mucoepidermoid carcinomas and its usefulness as an indicator in tumor progression, aggressiveness, and prognosis.

Methods: Thirty-one patients with mucoepidermoid carcinomas who had surgical resection were studied retrospectively. Clinicopathologic features, including histologic types, T stage, nodal status, perineural invasion, overall AJCC stage, and survival data, were obtained from medical records. Immunohistochemical staining with monoclonal antibodies against p27(Kip1) was performed on the formalin-fixed, paraffin-embedded specimens from each patient. The percentage of tumor cells expressing p27(Kip1) (labeling index) was evaluated by counting 1000 cells per slide in at least four different areas and comparing with the patients' clinicopathologic features and survival rates.

Results: Significant correlation was found between low p27(Kip1) expression and tumors with high-grade, advanced T stages, positive nodal status, and advanced clinical stages (p =.001 for all) except perineural invasion. Multivariate analysis indicated that p27(Kip1) expression (p =.030) was the most significant, and gender (p =.048) was the next significant predictor of overall survival among the variables. Also patients with low p27(Kip1) expression showed poor prognosis (p =.002).

Conclusions: We suggest that p27(Kip1) is a reliable independent marker of tumor progression, invasiveness, and prognosis in the mucoepidermoid carcinomas.