Downregulation of DLEC1 in Sinonasal Inverted Papilloma and Squamous Cell Carcinoma

Objective: Inverted papilloma is associated with sinonasal squamous cell carcinoma. This study aimed to investigate the epigenetic regulation of the tumour suppressor gene DLEC1 in inverted papilloma and sinonasal squamous cell carcinoma. Methods: DLEC1 gene expression was investigated by quantitative real-time polymerase chain reaction (QRT-PCR) in normal mucosa, inverted papilloma, and squamous cell carcinoma tissues. Methylation-specific PCR and subsequent autosequencing were also used to examine the methylation status of DLEC1 promoter and the involved mechanism. DLEC1 expression in a large validation set was evaluated by immunohistochemistry (n 5 25 in each group). Results: DLEC1 was downregulated in inverted papilloma and squamous cell carcinoma tissues compared to normal mucosa (p , .01 in QRT-PCR and immunohistochemistry), with squamous cell carcinoma more repressed (p , .05 in QRT-PCR and immunohistochemistry) than inverted papilloma tissues. DLEC1 promoter hypermethylation was found in squamous cell carcinoma tissues. Conclusion: Repression of DLEC1 in squamous cell carcinoma tissues is associated with promoter hypermethylation. DLEC1 is downregulated in sinonasal squamous cell carcinoma and inverted papilloma and has a distinct mechanism.