Epithelial proliferation markers in dysplasias and carcinomas associated with human papillomavirus

Abstract

Proliferative verrucous leukoplakia (PVL) is a disorder characterized by the progressive development of epithelial dysplasia eventuating in carcinoma. The majority of these lesions have been associated with human papillomavirus (HPV). The purpose of this study was to evaluate 2 epithelial proliferation markers in HPV-associated oral dysplasia and carcinoma to determine the level of epithelial activation and to assess the possibility of the epithelial marker-guided prediction of prognosis for patients with PVL. Forty archival cases of paraffin-embedded HPV-positive lesions diagnosed as either epithelial dysplasia, verrucous hyperplasia, verrucous carcinoma, or squamous cell carcinoma obtained from patients with the clinical presentation of PVL were retrieved from the files of the University of North Carolina Oral and Maxillofacial Pathology Laboratory. Controls consisted of epithelium surfacing irritation fibromas. Immunostaining with primary antibodies to epidermal growth factor (EGFr) and proliferating cell nuclear antigen was performed by using the avidin-biotin-peroxidase technique with diaminobenzidine as a chromogen. EGFr positivity was graded subjectively on a scale from 0 to 3+, whereas proliferating cell nuclear antigen positivity was evaluated by examining sections under 100× oil immersion and determining the ratio of labeled-to-unlabeled cells from a count of 1000 cells per section. The results revealed a mean of 0.53 PCNA labeling in controls and a mean of 0.72 in all experimental groups combined (t test: P < .0001). EGFr staining of lesional epithelium revealed similar elevation over controls. We conclude that these proliferation markers have potential as prognostic indicators of the progression of PVL.