Investigations to the influence of tumor supressor gene p16 inactivation on the prognosis of head and neck squamous cell carcinoma

Abstract

The inactivation of the tumor suppressor gene p16 plays an important role in the development of malignant tumors. P16 loss can result from point mutations, loss of heterozygosity (LOH) or methylation of the promoter region. A total of 67 samples of tumor tissue from squamous cell carcinomas of the oral cavity, the pharynx and the larynx were analysed for an inactivation of p16. The samples were obtained during surgery. In all cases there was a curative intention. Point mutations were detected by DNA sequencing. Methylation of the promotor region was explored with a methylation-specific PCR. A microsatellite analysis of the tumor tissue was used to search for LOH. The results of the molecularbiological investigations were correlated to the known clinical prognostic parameters (tumor stadium, grading, patho-histological differentiation, local and regional recurrence) after a follow-up period of approximately 3 years. Methylation of the promotor region and LOH were the main mechanisms of p16 inactivation encountered in this study. Point mutations presented as rare events. The methylation of the promotor region appeared frequently parallel with an LOH. An inactivation of p16 did not have any statistical influence on the tumor dependent survival, the lymphatic spread, the number and time delay of local and regional recurrences. Patients with an inactivated p16 gene by promotor methylation appeared to have a slightly lower tendency for local and regional recurrences. The inactivation of the tumor suppressor gene p16 plays a role in the carcinogenesis of squamous cell carcinomas of the oral cavity, the pharynx and the larynx. There is no influence on the tumor dependent prognosis. Tumors with an inactivated p16 gene tend to have a lower recurrence rate.