Methods: Forty CXPAs occurring in parotid glands and eight normal parotid glands were studied for p16INK4a alterations using immunohistochemistry (IHC) and methylation specific PCR (MSP) which have been followed up for 10 to 15 years. Survival was calculated by the Kaplan-Meier method, and prognostic variables were analyzed by the log-rank test.
Results: In normal parotid glands, p16INK4a protein was positively expressed in each case. Twenty-one cases (21/40, 52.5%) CXPAs showed decreased (in different degrees) or absent p16INK4a protein expression compared to normal parotid glands. The hypermethylation of p16INK4a gene promoter were found in 16 cases (16/40, 40%) of CXPAs which was not found in normal salivary glands. The survival rate of the patients with positive expression was higher than those with negative expression ( P < 0. 01) . Furthermore , the survival stage of the patients with positive expression was significantly elongated. Patients with hypermethylation of p16INK4a gene promoter had a shorter survival time than those without hypermethylation of p16INK4a gene promoter.
Conclusion: The expression levels of p16INK4a gene correlated significantly with the prognosis of patients with CXPA. Inactivation of p16INK4a gene by hypermethylation play an important role in CXPA and might be crucial for carcinogenesis in parotid gland.