Increased Expression of DNA Methyltransferase-1 in Non-Neoplastic Epithelium Helps Predict Colorectal Neoplasia Risk in Ulcerative Colitis

Abstract

Aims: To clarify the possible significance of increased expression of DNA methyltransferase (DNMT)-1 in the tumorigenesis of colorectal neoplasia in ulcerative colitis (UC) and to clarify whether analysis of DNMT1 expression in non-neoplastic epithelium can contribute to the prediction of increased risk for UC-associated neoplasia. Methods: Sixty-two patients with long-standing and extensive UC were included in this study: 31 with colorectal neoplasia (dysplasia in 11 and invasive cancer in 20) and 31 without. Immunohistochemical analysis and quantitative RT-PCR were performed to determine the expression of DNMT1 in rectal epithelium of UC patients without neoplasia, and in non-neoplastic rectal epithelium and colorectal neoplasia of UC patients with neoplasia. Results: The immunoreactive DNMT1 expression gradually increased from rectal epithelium of UC patients without neoplasia (0.13 ± 0.07) to non-neoplastic rectal epithelium of UC patients with neoplasia (0.32 ± 0.12, p < 0.001), and to colorectal neoplasia (0.54 ± 0.20, p < 0.001). Among 31 neoplasias, there was no difference in the immunoreactive DNMT1 expressions between dysplasia and invasive cancer (0.47 ± 0.52 vs. 0.58 ± 0.63). The expression level of DNMT1 mRNA tended to increase gradually from rectal epithelium of UC patients without neoplasia (0.53 ± 0.34) to non-neoplastic rectal epithelium of UC patients with neoplasia (0.88 ± 0.57, p = 0.06), and to colorectal neoplasia (1.38 ± 0.64, p = 0.07). Conclusion: Increased expression of DNMT1 in non-neoplastic epithelium may precede or be a relatively early event in UC-associated tumorigenesis, and may help predict the risk of colorectal neoplasia in UC.