Hypermethylation status of E-cadherin and p16INK4a in gastrointestinal stromal tumor

Abstract

To investigate the methylation status of CpG island in E-cadherin(CDH 1 ), P16INK4a(P16) promoter region,and to analyze their role in gastrointestinal stromal tumor (GISTs). A total of 56 surgically resected GISTs were obtained from January 2003 to December 2005. The routine H&E-stained sections and CD117, CD34-immunoreactions were reviewed to verify the morphologic diagnosis. Methylation status of the CDH 1 , P16INK4a promoter region was analyzed by methylation specific polymerase chain reaction (MSP) from chemically modified DNA after Na-bisulfite treatment. The frequency of CDH 1 gene methylation was 32% (18 of 56) in GISTs. The rate was 9% (1 of 11), 21% (4 of 19), 41.6% (5 of 12), and 57% (8 of 14) for very low risk, low risk, intermediate risk, and high risk GISTs; P16 INK4a methylation was found in 19 of 56(34%) cases. The rate was 0% (0 of 11), 16% (3 of 19), 50% (6 of 12), and 71% (10 of 14) for very low risk, low risk, intermediate risk, and high risk GISTs. Statistical analysis indicated that of the 56 cases, there was significant association of CDH 1 and/or P16 INK4a methylation status with tumor malignant behavior (methylation rate 23/56, 41%, P<0.01) and site (P<0.05). E-cadherin (CDH 1 ) and/or P16 INK4a promoter hypermethylation is strongly associated with risk grade, may be a useful biomarker for GISTs risk assessment, and may shed light on new therapeutic options to treat GISTs