Expression of inhibitor of apoptosis family proteins in human oral squamous cell carcinogenesis.

BACKGROUND The purpose of this study was to determine inhibitor of apoptosis (IAP) expression, its relationship with p53, and epigenetic change in oral carcinogenesis that remain to be elucidated. METHODS We measured IAP and p53 expression in 44 oral potentially malignant disorders and their corresponding malignant-transformed oral squamous cell carcinomas (OSCCs), and in 44 other non-transformed oral potentially malignant disorders. IAP and p53 expression in 10 fresh OSCCs, together with epigenetic change of their mutation, were also determined. RESULTS Normal mucosa did not express IAP/mutated p53. Oral potentially malignant disorders that underwent transformation exhibited high IAPs (>90%) and less-consistent mutated-p53 (34%) expression, whereas transformed OSCCs exhibited high IAP and mutated-p53 expression. Fresh OSCCs exhibited 80% to 100% IAP mRNA expression and 50% protein, mRNA, and p53 mutation expression. Normal tissues revealed DNA methylation of IAP, whereas cancerous tissues overexpressing IAP exhibited hypomethylation. CONCLUSION This study showed that IAP expression is an early event in oral carcinogenesis and that epigenetic and genetic pathways are associated with IAP expression in OSCC.