Telomerase activation cooperates with inactivation of p16 in early head and neck tumorigenesis

Alteration of the p16/pRb pathway may cooperate with telomerase activation during cellular immortalization and tumour progression. We studied p16 expr ession status by immunohistochemistry and telomerase activity using the TRA P assay in 21 premalignant lesions of the head and neck epithelium as well as 27 squamous-cell carcinomas. We also examined expression of other compon ents of the pathway (cyclin D1 and pRb) as well as presence of human papill omavirus genomes which can target these molecules. 4 of 9 mild dysplastic l esions (44%), 8 of 12 moderate/severe dysplastic lesions (67%), and 25 of 2 7 squamous-cell carcinomas (92%) demonstrated high telomerase activity (P = 0.009), There was a parallel increase with severity of lesions for the tre nd in proportions of cases demonstrating p16 inactivation or cyclin D1 over expression (P = 0.02 and P = 0.01. respectively). For Ki67, a marker of cel l proliferation, this trend was not significant (P = 0.08). Human papilloma virus infection was only found in 4 cases among the 48 samples tested (8.3% ). In conclusion, progression of disease is accompanied by a parallel and c ontinuous increase in telomerase activity and alterations in cell cycle reg ulators (p16, cyclin D1), as proposed by in vitro models. (C) 2001 Cancer R esearch Campaign.