In situ analysis of p16/INK4 promoter hypermethylation in esophageal carcinoma and gastric carcinoma

Authors: Fan ZHANG1; Li WANG1; Ping Ping WU1; Zhao Wen YAN1; Lin ZHENG1; Ying Yan YU2; Xu Cheng JIANG

Source: Chinese Journal of Digestive Diseases, Volume 5, Number 4, December 2004 , pp. 149-155(7)

Publisher: Wiley-Blackwell

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Abstract:

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. CONCLUSION:

The role of DNA methylation in the silence of p16/INK4 may different between these two types of upper digestive tract tumor.

Keywords: carcinoma; DNA methylation; esophagus; p16; stomach

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1443-9573.2004.00172.x

Affiliations: 1: Department of Pathology, Shanghai Second Medical University 2: Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Second Medical University, Shanghai, China

Publication date: 2004-12-01

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