Potential Diagnostic Use of p16INK4A, a New Marker That Correlates With Dysplasia in Oral Squamoproliferative Lesions

Abstract

Protein products of tumor suppressor genes are often involved in regulating the cell cycle, and aberrant expression can correlate with underlying genetic mutations. Mutations in the p16 gene have been detected at relatively high rates in squamous cell carcinomas of the oral cavity. However, immunohistochemical staining for the protein product has not been examined as a diagnostic tool for identifying dysplastic lesions in the oral cavity. Sixty cases of biopsies of reactive, inflammatory, and dysplastic lesions of all grades were stained with an antibody to p16INK4A and analyzed for which layer of the epithelium had positive cells. Staining was seen only in the basal or lower third in keratoses and mild dysplasias and was seen in the mid and upper thirds in moderate to severe dysplasia. The staining across larger fragments of biopsied epithelium highlighted skip lesions, with strong staining restricted to dysplastic regions. Inflammatory lesions, including chronic ulcers, showed absent or minimal basal layer staining with p16INK4A. In this preliminary study, p16INK4A shows promise as to a potential marker to aid in recognizing the presence of dysplasia in squamous mucosa of the head and neck, particularly in subtle lesions, and in an inflammatory or ulcerated background.