Methylation of the oestrogen receptor gene in non- neoplastic epithelium as a marker of colorectal neoplasia risk in long-standing and extensive ulcerative colitis

Shigehiko Fujii ¹, Keiichi Tominaga ², Kazuaki Kitajima ², Jun Takeda ², Toshihiro Kusaka ³, Mikio Fujita ², Kazuhito Ichikawa ², Shigeki Tomita ², Yasuo Ohkura ², Yuko Ono ², Johji Imura ², Tsutomu Chiba ³ and Takahiro Fujimori ^2*

¹ Dokkyo University School of Medicine and Kyoto University, Postgraduate School of Medicine, Japan
² Dokkyo University School of Medicine, Japan
³ Kyoto University, Postgraduate School of Medicine, Japan

^* To whom correspondence should be addressed. E-mail: t-fuji{at}dokkyomed.ac.jp.

Accepted 26 April 2005

Abstract

Background: Surveillance colonoscopy is widely recommended in patients with long-standing and extensive ulcerative colitis (UC), in order to detect colorectal neoplasia at an early stage. However, it still remains questionable whether surveillance colonoscopy effectively enables early detection of UC-associated neoplasia. There is a great need for sensitive markers to identify individuals at increased risk of neoplasia. The estrogen receptor (ER) gene shows age-related methylation in the colorectal epithelium and is methylated frequently in sporadic colorectal neoplasia, suggesting that ER methylation might predispose to colorectal neoplasia.

Aim: To clarify whether analysis of methylation of the ER gene in non-neoplastic epithelium can contribute to the prediction of increased neoplasia risk in UC patients.

Materials and Methods: A total of 165 non- neoplastic colorectal epithelia from 30 patients with long-standing and extensive UC, including 13 UC patients with neoplasia and 17 patients without, were evaluated. Methylation-specific PCR was performed to determine the methylation status of the ER gene.

Results: Methylation of the ER gene was detected in 54 of 70 (77.1%) non-neoplastic colorectal epithelia in UC with neoplasia, whereas in only 23 of 95 (24.2%) without neoplasia. Methylation of the ER gene was significantly more frequent in non-neoplastic epithelium from UC with neoplasia than in chronic colitic epithelium from UC without neoplasia. In UC with neoplasia, furthermore, the ER gene was extensively methylated in non-neoplastic epithelia throughout the colorectum as compared with those in UC without neoplasia.

Conclusion: These results suggest that analysis of ER gene methylation may have potential to be useful marker for identifying individuals at increased risk of neoplasia among patients with long-standing and extensive UC.

Keywords: UC-associated neoplasia, methylation, oestrogen receptor

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