p16^INK4a, and p14^ARF Expressions in Carcinogenesis of Squamous Cell Carcinoma of the Lip

The goal of this study was to clarify the role of p16^INK4a, p14^ARF, and p53 protein expressions in carcinogenesis in squamous cell carcinomas of the lip. The expressions of the p53, p16^INK4a, and p14^ARF proteins were examined in 46 formaline-fixed paraffin embedded tissue specimens, which included 19 cases of squamous cell carcinoma of the lip, 14 cases of actinic cheilitis, and 13 cases of normal mucosa. Immunoreactivity in the peritumoral epithelium adjacent to squamous cell carcinomas was also evaluated. p16^INK4a expression was increased in actinic cheilitis in comparison with normal mucosa (p=0.001). p14^ARF expression progressively increased from normal mucosa to actinic cheilitis (p=0.001) and was observed to decrease significantly during the process of transition from actinic cheilitis to carcinoma (p=0.003). p53 values progressively increased from normal mucosa to actinic cheilitis (p=0.001) and carcinoma (p=0.008). A significant positive correlation was found between p14^ARF and p53 in the peritumoral epithelium adjacent to carcinomas. Our findings indicated that p16^INK4a and p14^ARF immunohistochemistry does not determine whether or not actinic cheilitis has the potential to develop carcinoma. The p14^ARF /p53 pathway is activated in the peritumoral epithelium adjacent to carcinoma; however, this activation would not be adequate to prevent carcinogenesis.