Expression of Cyclin-dependent Kinases Inhibitors p21(WAF1)and p27(KIP1) in Benign, Premalignant and Malignant Laryngeal Lesions. Correlation with Cell Cycle Regulatory Proteins

Abstract

Background: Cell cycle progression and transition of cells from the first gap phase (G1) to the DNA replication phase (S) depend on a finely tuned balance between the levels of cyclins, cyclin-dependent kinases (CDKs) and cyclin-dependent kinase inhibitors (CDKIs). Materials and Methods: We analyzed 57 squamous cell invasive carcinomas of the larynx, 10 in situ carcinomas, 56 cases of dysplasia, 11 papillomas and 26 keratosis. We investigated: a) the immunohistochemical expression of CDKIs, p21 and p27, b) any possible relation between normal and abnormal immunoprofiles of these proteins and p53 protein and proliferation status as determined by the expression of Ki67 and PCNA, and c) their presence in pre-malignant and malignant laryngeal lesions. Results: Expression of p21 and p27 was observed in 58.9% and 89.5% of the laryngeal carcinomas, respectively. High levels of p21 were significantly correlated with increased cyclin D (p=0.001), cyclin E (p<0.001) and Ki67 (p<0.001), while increased expression levels of p27 were associated with p53 accumulation (p=0.02) and with increased proliferation status as expressed by Ki67 (p=0.05). Conclusion: Due to the increased expression levels of CDKIs in laryngeal carcinomas, we suggest the existence of a mechanism by which tumor cells tolerate the inhibitory effect of these proteins on cell cycle progression.