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Hypermethylation of the somatostatin promoter is a common, early event in human esophageal carcinogenesis

✍ Scribed by Zhe Jin; Yuriko Mori; James P. Hamilton; Alexandru Olaru; Fumiaki Sato; Jian Yang; Tetsuo Ito; Takatsugu Kan; Rachana Agarwal; Stephen J. Meltzer

Publisher: John Wiley and Sons
Year: 2007
Tongue: English
Weight: 235 KB
Volume: 112
Category: Article
ISSN: 0008-543X
DOI: 10.1002/cncr.23135

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

BACKGROUND.

The promoter of somatostatin (SST), a primary inhibitor of gastrin‐stimulated gastric acid secretion, is hypermethylated in 80% of human colon cancers. The aim of the current study was to investigate whether and at what stage promoter hypermethylation of SST is involved in human esophageal carcinogenesis.

METHODS.

SST promoter hypermethylation was examined by real‐time methylation‐specific polymerase chain reaction (PCR) (MSP) in 260 human esophageal tissue specimens. Real‐time reverse‐transcriptase PCR and MSP were also performed on esophageal cancer cell lines before and after treatment with 5‐aza‐2′‐deoxycytidine (5‐Aza‐dC).

RESULTS.

SST hypermethylation showed highly discriminative receiver‐operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinomas (ESCC) and esophageal adenocarcinomas (EAC) from normal esophagus (NE) (P < .01). Both SST methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett metaplasia without dysplasia or EAC (BE), low‐grade and high‐grade (HGD) dysplasia occurring in BE, EAC, and ESCC than in NE (P < .01). SST hypermethylation frequency was significantly lower in NE (9%) than in BE (70%), HGD (71.4%), or EAC (71.6%), whereas 14 (53.8%) of 26 ESCCs exhibited SST hypermethylation. There was a significant relation between SST hypermethylation and BE segment length, a known clinical risk factor for neoplastic progression. Demethylation of KYSE220 ESCC and OE33 EAC cells with 5‐Aza‐dC reduced SST methylation and increased SST mRNA expression. SST mRNA levels in native unmethylated EACs were significantly higher than in native methylated EACs (P < .05).

CONCLUSIONS.

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