Analysis and comparison of podoplanin (D2-40) and p53 as potential predictors of malignant progression in proliferative verrucous leukoplakia (PVL)

Abstract

<h3>Introduction</h3> p53 overexpression is well documented in premalignant lesions of the oral cavity. However, recent studies have shown increased expression of podoplanin (D2-40) in oral dysplasia. This study aims to evaluate the efficacy of both markers in predicting malignant transformation in cases of proliferative verrucous leukoplakia (PVL), a recalcitrant oral premalignant condition with a high rate of malignant transformation. <h3>Materials and methods</h3> With IRB approval the UF archives were searched from 1994-2019 for cases with clinical diagnosis of PVL with at least one biopsy and follow-up of at least 3 years. Included cases were tested for IHC reactivity to p53 and D2-40. Reactivity was evaluated for basal cell layer nuclear positivity to p53 and cytoplasmic positivity to D2-40. Results for both tests were recorded as either >25% or <25% positivity in the basal cell layer. <h3>Results</h3> A total of 17 cases were included. The mean age was 63.11 years and 76.4% of the patients were females. Locations included gingiva (59%), tongue (17%), buccal mucosa (12%), palate and floor of the mouth (6% each). The histological diagnoses included verruco-papillary hyperkeratosis/verrucous hyperplasia (59%), atypia/dysplasia (18%), hyperkeratosis (17%), and atypical epithelial proliferation (6%). Of the included cases, 7 (41%) subsequently developed malignancy. There was no statistically significant difference in terms of age, gender, location, or histologic diagnosis regarding either p53 or D2-40 positivity. There was no significant difference between p53 positivity between cases with or without malignant transformation; however, cases with subsequent malignant transformation demonstrated significantly higher positivity to D2-40 than those that did not transform (<i>p=0.006</i>, chi-square). <h3>Conclusion</h3> D2-40 IHC testing was more useful in predicting malignant transformation than p53 in this small sample of PVL cases. Additional larger scale studies will likely confirm utility of D2-40 IHC testing in predicting PVL progression.