In situ analysis of p16/INK4 promoter hypermethylation in esophageal carcinoma and gastric carcinoma.
OBJECTIVE
Inactivation of the tumor suppressor gene by CpG hypermethylation is a common event in a variety of tumors. The present study was designed to be a comprehensive analysis of p16/INK4 methylation in carcinomas of the upper digestive tract.


METHODS
Series of esophageal carcinomas (34 cases) and gastric carcinomas (25 cases) were examined for CpG methylation in p16/INK4 using methylation-specific PCR (MSP). The tissue sections underwent MSP in situ and were then examined microscopically. Immunohistochemical detection of the expression of p16 in the tumor specimens was also performed.


RESULTS
Immunohistochemistry detected positive p16 expression in 8 cases of esophageal squamous cell carcinoma and 15 cases of gastric carcinoma. In esophageal carcinoma, hypermethylation of the p16/INK4 promoter region was detected in 5 cases without statistical correlation with its loss of expression, whereas in the gastric carcinomas, p16 expression was positively correlated with the T-classification (r = 0.488, P = 0.01); p16/INK4 methylation was identified in 8 cases. In addition, p16 expression was lower in the methylated samples than in the non-methylated samples (25% vs 76.47%, P = 0.03). Analysis of the MSP-in-situ sections showed that the distribution of methylated cells in esophageal carcinoma differed from that in gastric carcinoma.


CONCLUSIONS
The role of DNA methylation in the silence of p16/INK4 may different between these two types of upper digestive tract tumor.
Zhang
Fan
F
Department of Pathology, Shanghai Second Medical University, Shanghai, China.
Wang
Li
L
Wu
Ping Ping
PP
Yan
Zhao Wen
ZW
Zheng
Lin
L
Yu
Ying Yan
YY
Jiang
Xu Cheng
XC
D002277:Carcinoma / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000235:genetics*; D019942:Genes, p16; D006801:Humans; D007150:Immunohistochemistry; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics*
D019941:Cyclin-Dependent Kinase Inhibitor p16