Methylation of p16 gene and reduced expression of p16 protein in insulinoma associated with clinicopathological features

Abstract

Objective: To study the alterations of p16 gene and its expression in insulinoma and to correlate the findings with clinicopathological characteristics. Methods: Expression of p16 protein was detected in 72 insulinomas and 49 para-tumoral or normal pancreatic tissues by immunohistochemical staining. Genomic DNA was isolated from 32 tumor tissue and 17 paired pancreatic tissues and bisulfite-modified. Promoter methylation status of p16 gene was detected in 32 tumor tissue and 17 paired pancreatic tissues by methylation specific PCR. The findings were correlated with the clinicopathological features. Results: There were 30 males and 42 females in all 72 patients, aged (46.5±14.0) years. Loss or reduced expression of p16 protein was found in 42 of 72 insulinomas (58.3%) while loss or reduced expression of p16 was seen in only 34.7% (17/49) of para-tumoral or normal pancreatic tissues (χ²=6.52, P=0.011). Promoter methylation of p16 gene was found in 13 of 32 insulinomas (40.6%) and only 2 of 17 (11.8%) para-tumoral tissues (χ²=4.35, P=0.037). The expression of p16 protein in insulinoma was not associated with clinicopathological features such as gender, age, tumor size and tumor grade. Conclusions: Loss or reduced expression of p16 protein was found in insulinomas, and associated with p16 gene promoter methylation.