p16 Alterations and retinoblastoma protein expression in squamous cell carcinoma and neighboring dysplasia from the upper aerodigestive tract

The progression potential of preinvasive epithelial lesions is usually eval uated by assessing the degree of histologic dysplasia. We examined p16, ret inoblastoma protein (pRb), and proliferating cell nuclear antigen (PCNA) im munophenotypes in 57 cases of previously untreated squamous cell carcinoma (SCC) of the upper digestive tract and in the neighboring normal and dyspla stic epithelia. Tissue samples were examined for homozygous deletion of exo n 2 of the p16 gene using polymerase chain reaction (PCR) analysis. The PCN A index increased with increasing grade of dysplasia. The pRb protein was e xpressed in 89% of the samples of SCCs and in the neighboring dysplasias an d carcinoma in situ (CIS). In cases with a lack of pRb expression, correspo nding preinvasive lesions were also negative. Lack of p16 expression was fo und in 82% of SCCs. The prevalence of p16 expression decreased with increas ing grade of dysplasia. Molecular analysis of the p16 gene showed homozygou s deletion in 37% of SCCs, 33% of CIS, and 15% of the samples of normal epi thelia. Our data indicate that inactivation of p16 may play an important ro le in early head and neck carcinogenesis, whereas the mutation of Rb may be an infrequent event. The p16 immunophenotype might be a biomarker for an i ncreased risk of progression in squamous dysplasia.