Purpose: The incidence of colorectal neoplasia has increased among patients with longstanding and extensive ulcerative colitis (UC).Therefore, surveillance colonoscopy has been widely recommended. However, there is controversy about the impact of cancer surveillance, and ways to improve its effectiveness are being sought. The estrogen receptor (ER) gene shows age-related methylation in the colorectal epithelium and is frequently methylated in colorectal neoplasia, suggesting that ER methylation occurs early in the process of colorectal tumorigenesis. Experimental Design: To clarify whether methylation analysis of the ER gene in nonneoplastic epithelium can help predict an increased risk for UC-associated neoplasia, a total of 105 nonneoplastic colorectal epithelia from 18 patients with longstanding and extensive UC, including 8 patients with neoplasia and10 patients without neoplasia, were analyzed. In all patients, multiple samples were taken from six regions of the colorectum.The combined bisulfite restriction analysis method was used to determine the methylation status of the ER gene. Results: The mean methylation level of the ER gene was 25.4% in the nonneoplastic epithelia from UC patients with neoplasia, whereas it was only 4.0 % in those without neoplasia (P < 0.001). The methylation level of the ER gene in UC patients with neoplasia was significantly higher than in UC patients without neoplasia throughout the colorectum except for the cecum. In UC patients with neoplasia, the mean ER methylation level in the distal colon (36.1%) was significantly higher than in the proximal colon (14.6%; P < 0.001).Conclusions: These results suggest that the analysis of ER gene methylation in nonneoplastic colorectal epithelium could have the potential to be a useful adjunct for identifying individuals with longstanding and extensive UC who are at increased risk of neoplasia and contribute to more effective cancer surveillance.

These results show that LST-G and LST-NG have different genetic alterations.

Necl‐5 is an immunoglobulin‐like molecule that was originally identified as a poliovirus receptor. Although Necl‐5 expression is often up‐regulated in cancer cells, its pathophysiological significance in the development of cancer remains unclear. We investigated the roles of Necl‐5 in the development of colitis‐associated neoplasia. Necl‐5‐deficient mice were generated and treated with dimethylhydrazine (DMH) and/or dextran sodium sulphate (DSS) to induce colitis and its associated neoplasias. Colon tissues were examined for histology, Ki‐67 expression by immunohistochemistry and K‐ras gene mutation. Colon tumours occurred significantly less frequently in heterozygous (Necl‐5+/−) or homozygous Necl‐5‐deficient (Necl‐5−/−) mice than in wild‐type (WT) mice with DMH/DSS treatment. Total ulcer index and inflammatory cell infiltration were significantly lower in Necl‐5−/− mice than in WT mice with DSS alone or DMH/DSS treatment. Colon tumours in both WT and Necl‐5−/− mice showed high cell proliferation ability but lacked K‐ras mutation. The total Ki‐67 labelling index in non‐neoplastic colon epithelium was significantly higher in WT (45.9 ± 0.94) than in Necl‐5+/− (34.3 ± 1.40) or Necl‐5−/− (27.7 ± 1.15) mice with DMH/DSS treatment (p < 0.001). Necl‐5 plays a role in the development of colitis‐associated cancer by up‐regulating colonic mucosal cell proliferation. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Both COX-2 and VEGF are involved in tumor vascularization in CRC-sm. COX-2 expression, VEGF expression, and MVD are possible markers for predicting lymph node metastasis in patients with CRC-sm, and use of COX-2 expression may be clinically practical.