Utility of p53, p16, and MTAP Immunohistochemistry in Oral Epithelial Dysplasia With Concurrent Candidiasis: A Novel...

The diagnosis of oral epithelial dysplasia has a high degree of inter- and intraobserver variability. It is especially challenging to distinguish dysplasia from reactive squamous mucosa in the context of concurrent candidiasis. The accurate and timely diagnosis of dysplasia is imperative for patient outcomes, as progression to invasive squamous cell carcinoma will result in significant morbidity and mortality. The current management for patients with candidiasis is to treat with antifungals and rebiopsy if refractory. The treatment may be trialed for a few months, thus delaying appropriate treatment if underlying dysplasia is not identified. In this study, we collected cases of oral candidiasis with atypia and characterized them into molecularly defined groups using targeted next-generation sequencing, fluorescence in situ hybridization, and p53, p16, and MTAP immunohistochemistry. We identify a distinct molecular signature using immunohistochemical markers to capture oral dysplasia with concurrent candidiasis. We also postulate that p53 wild-type, p16 abnormal oral epithelial dysplasia cases are precursor lesions to p53 wild-type, p16 abnormal squamous cell carcinoma. In addition, we identify p53 wild-type, p16 wild-type oral epithelial dysplasia with verruciform and acanthotic features with HRAS or PIK3CA alterations as precursors to verrucous carcinoma. The proposed pattern-based p16 and p53 algorithm in our study will not only more accurately diagnose dysplasia in the context of oral candidiasis but may also provide prognostically significant information to guide clinical management of oral dysplastic lesions.