Upper aerodigestive tract squamous dysplasia correlation with p16, p53, pRb, and Ki-67 expression

Abstract

Context. - Differential expression of cell cycle-associated proteins may correlate with human papillomavirus status and may help delineate degree of dysplasia in upper aerodigestive tract squamous lesions. Objective. - To determine intraepithelial height of immunohistochemical staining for p16, p53, pRb, and Ki-67 in upper aerodigestive tract lesions with reference to degree of dysplasia. Human papillomavirus status was ascertained to correlate with p16 expression. Design. - Biopsy specimens of 53 squamous dysplastic and 13 keratotic/hyperplastic lesions were immunohistochemically stained for p16, p53, pRb, and Ki-67. Mean height and proportion of positive staining were quantified and compared for keratotic/hyperplastic, mild, moderate, and severe dysplasia/carcinoma in situ. DNA extracted from paraffin-embedded blocks was evaluated for human papillomavirus by polymerase chain reaction amplification using consensus primers for mucosal viral types. Results. - Height of Ki-67 staining within the epithelium increased significantly between mild and moderate and between mild and severe dysplasia, with a trend toward increasing height between moderate and severe dysplasia. The percentage of cases with p16 staining decreased significantly with increasing degree of dysplasia; however, no significant trend in staining height or proportion was observed with p16, p53, or pRb in relation to degree of dysplasia, or 0between dysplastic and keratotic/hyperplastic lesions. Only 1 of 53 dysplastic lesions was positive for human papillomavirus. Conclusions. - This series of upper airway dysplastic mucosal lesions demonstrated a positive correlation between intraepithelial Ki-67 staining height and degree of dysplasia, offering a diagnostic aid in delineating degree of dysplasia in difficult squamous lesions.