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

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.

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.

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.

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 between dysplastic and keratotic/hyperplastic lesions. Only 1 of 53 dysplastic lesions was positive for human papillomavirus.

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.