The Cell Cycle Regulators and Cyclin D1: Relationship to Clinicopathological Parameters and Disease-free Survival in Laryngeal Carcinoma Patients.

Laryngeal squamous cell carcinoma (LSCC) is a frequent malignancy with a complex and undefined etiology to date. The recently identified cyclin-dependent kinase inhibitor p15 is frequently deleted in human tumors. Previous evidence has pointed to a related gene, p16, as another target for deletion. Both genes express cyclin D inhibitor proteins. To determine the importance of cell cycle regulators in LSCC relative to more traditional surgical and pathological prognostic factors, p15, p16 and cyclin D1 analyses were performed. Forty-one malignant tumor tissues and 20 minimal pathological lesions (MPL) of the larynx were examined for deletion of the p16 and p15 genes using polymerase chain reaction. Cyclin D1 expression was studied by Western blotting. Deletions of p16 and p15 were observed in 48.8 % and 51.2% of LSCC patients, respectively. Meanwhile, no deletion was observed in MPL (p<0.001). Cyclin D1 was expressed in 43.9% of patients with LSCC versus 30% with MPL (p=0.29). Although the frequency of p16 and p15 deletions were higher in advanced than early tumor stages, the difference was statistically insignificant. Ninety percent of patients with deletion of p16 had deletion of the p15 gene. Both cyclin D1 expression and deletion of p15 were found to be independent prognotic predictors of disease recurrence. p16 and p15 gene deletions are exclusively related to malignancy of the larynx. Cyclin D1 expression and p15 gene deletion are potential prognostic indicators of recurrence of LSCC.