Comparative Pilot Study of Chronic Hyperplastic Candidiasis and Atypical Epithelial Proliferation With Candida Utilizing p53, p16, CD44 , and OCT4

ABSTRACT Introduction Chronic hyperplastic candidiasis (CHC) has a controversial potential role in the carcinogenesis of oral epithelium. In addition, histological overlap between CHC and atypical epithelial proliferation with Candida (AEPC) may cause a diagnostic dilemma. In this pilot study, potential premalignant markers including tumor suppressor gene proteins p53 and p16, and cancer stem cell markers CD44 and OCT4, were investigated in CHC and AEPC with benign and malignant validation groups. Materials and Methods A total of 20 tongue lesions were identified, with 5 cases of each: benign validation group of traumatic fibroma, CHC without dysplasia, AEPC, and malignant validation group of moderately differentiated squamous cell carcinoma (SCCA). IHC staining was performed with p53, p16, CD44, and OCT4. Inter‐observer variability between two pathologists' independent scores was determined using Cohen's kappa ( k ). A third pathologist served as tiebreaker for disagreement. Chi‐square testing was performed between diagnostic groups and staining results. Results Overall agreement of staining for all stains was good ( κ  = 0.614) for intensity, moderate ( κ  = 0.544) for percentage, and good ( κ  = 0.612) for p53 wild or atypical pattern analysis (based on prior studies). p53 and CD44 staining showed statistically significant differences between the fibroma/CHC cases and the AEPC/SCCA cases. The most diagnostic measures were p53 pattern, which categorized 100% of fibroma/CHC cases as wild type and 90% of AEPC/SCCA groups as atypical ( p  < 0.001), and CD44 staining above 50%, which diagnosed 70% of AEPC/SCCA cases versus 0% of fibroma/CHC cases ( p  = 0.004). Using these two together, all AEPC/SCCA cases were diagnosed. p16 and OCT4 were not significant in differentiating between diagnoses in this study. Conclusions In this pilot study, p53 pattern and CD44 percentage showed significant potential to serve as useful diagnostic aids. Future studies with larger sample sizes are necessary to validate these findings and explore the potential of these markers in determining the transformation risk of CHC and AEPC.