ALTERATIONS OF P53, CYCLIN D1, RB, AND H-RAS IN HUMAN ORAL CARCINOMASRELATED TO TOBACCO USE

BACKGROUND, Epidemiologic studies have indicated that environmental an d personal habits, particularly tobacco use and alcohol abuse, are maj or etiologic factors in the induction and progression of head and neck squamous cell carcinomas (HNSCC). Molecular studies have focused on H NSCC related to smoking but not those associated with smokeless tobacc o. METHODS. The authors studied immunohistochemical evidence of altera tions of p53, cyclin D1, and Rb in 34 human oral carcinomas related to tobacco use. They also examined p53 and H-ras using single strand con formation polymorphism (SSCP) and sequencing analysis. RESULTS. Overex pression of cyclin D1 was found in 41% of cases, and accumulation of p 53 was found in 59%. Only 9% of the samples did not show Rb staining. In SSCP and sequencing analysis, 17 cases showed mutations in the cons erved region of the p53 gene. No mutations were detected in codons 12, 13, or 61 of the H-ras gene. CONCLUSIONS. Overexpression of cyclin D1 and p53 mutations are common alterations in HNSCC. In contrast, the l oss of Rb function Seems to occur infrequently, and mutations in the H -ras gene apparently do not play a role in this cancer. HNSCC associat ed with smokeless tobacco contained the same alterations as those rela ted to smoking. Cancer 1998;83:204-12. (C) 1998 American Cancer Societ y.