Molecular and histopathological findings in malignant transformation of proliferative verrucous leukoplakia that was successfully controlled for 15 years

This study aimed to identify new molecular and histopathological features of the malignant transformation of proliferative verrucous leukoplakia (PVL), which grows verrucously into verrucous carcinoma (VC) and/or squamous cell carcinoma (SCC) with malignant transformation potential different from that of common leukoplakia. Wnt-related oncogenes were analyzed by real-time quantitative PCR using excised specimens from a PVL patient who was successfully controlled for 15 years. The resected specimens, including normal-to-verrucous lesions, were examined immunohistochemically and evaluated for beta-catenin, p63, and p53 expression. Histopathological examination revealed verrucous hyperplasia in the left upper-lip mucosa and SCC in the left buccal mucosa; p53 and p21 expression was higher in the left upper-lip mucosa than in the normal oral mucosa, whereas HDM2, Axin2, and ref 1 expression was lower in the upper-lip mucosa than in the normal oral mucosa. p53 and HDM2 expression was higher in SCC than in normal oral mucosa, while p21, Axin2, and ref 1 was lower than those in normal oral mucosa. SCC showed higher expression of p53 and HDM2 than the normal oral mucosa. In transitional lesions of the left upper-lip mucosa, beta-catenin accumulated transiently in the cytoplasm, with no regularity of cell morphology and basement membrane continuity. However, for verrucous lesions, cell morphology and intercellular adhesion were preserved, and beta-catenin was localized almost exclusively to the plasma membrane. In this case, p53-p21 signaling suppressed carcinogenesis in the precancerous stage, suggesting that high-grade carcinogenesis by epithelial-mesenchymal transition-mediated beta-catenin-Wnt signaling did not occur in transition lesions.