PURPOSE: Making a clinicopathological diagnosis of dysplasia is crucial. We herein assess the significance of the DNA methyltransferase 3b (DNMT3b) expression as a diagnostic marker of ulcerative colitis (UC)-associated neoplasia. METHODS: Thirty-one patients with long-standing and extensive UC were included in this study. The expression of DNMT3b in non-neoplastic rectal epithelium (non-dysplasia in 31 patients) and colorectal neoplasia (dysplasia in 43 patients and invasive cancer in 34 patients) was determined using immunohistochemistry. The presence of immunoreactive DNMT3b was assessed in the areas with the highest density of cells with positively staining nuclei. DNMT3b was expressed as the percentage of positive cells relative to the total number of cells counted under high power magnification. RESULTS: The DNMT3b expression in neoplastic rectal epithelium (0.76, range 0.59-0.84) was increased compared to that observed in non-neoplastic epithelium (0.32, range 0.18-0.67, P < 0.001). A ROC curve analysis confirmed 0.68 to be the best diagnostic cut-off value for the DNMT3b expression in neoplastic epithelium (area under the curve = 0.810). The sensitivity of the diagnostic test was 66.2 %, the specificity was 86.7 %, the positive predictive value was 95.7 % and the negative predictive value was 36.1 %. The positive likelihood ratio was 4.98 and the negative likelihood ratio was 0.20. The accuracy was 69.9 %. CONCLUSIONS: An immunohistochemical analysis of the DNMT3b expression was associated with significant improvements in the discrimination of UC-associated neoplastic lesions.
PURPOSE: Making a clinicopathological diagnosis of dysplasia is crucial. We herein assess the significance of the DNA methyltransferase 3b (DNMT3b) expression as a diagnostic marker of ulcerative colitis (UC)-associated neoplasia. METHODS: Thirty-one patients with long-standing and extensive UC were included in this study. The expression of DNMT3b in non-neoplastic rectal epithelium (non-dysplasia in 31 patients) and colorectal neoplasia (dysplasia in 43 patients and invasive cancer in 34 patients) was determined using immunohistochemistry. The presence of immunoreactive DNMT3b was assessed in the areas with the highest density of cells with positively staining nuclei. DNMT3b was expressed as the percentage of positive cells relative to the total number of cells counted under high power magnification. RESULTS: The DNMT3b expression in neoplastic rectal epithelium (0.76, range 0.59-0.84) was increased compared to that observed in non-neoplastic epithelium (0.32, range 0.18-0.67, P < 0.001). A ROC curve analysis confirmed 0.68 to be the best diagnostic cut-off value for the DNMT3b expression in neoplastic epithelium (area under the curve = 0.810). The sensitivity of the diagnostic test was 66.2 %, the specificity was 86.7 %, the positive predictive value was 95.7 % and the negative predictive value was 36.1 %. The positive likelihood ratio was 4.98 and the negative likelihood ratio was 0.20. The accuracy was 69.9 %. CONCLUSIONS: An immunohistochemical analysis of the DNMT3b expression was associated with significant improvements in the discrimination of UC-associated neoplastic lesions.
Authors: T A Brentnall; D A Crispin; P S Rabinovitch; R C Haggitt; C E Rubin; A C Stevens; G C Burmer Journal: Gastroenterology Date: 1994-08 Impact factor: 22.682
Authors: Katsuhiko Nosho; Kaori Shima; Natsumi Irahara; Shoko Kure; Yoshifumi Baba; Gregory J Kirkner; Li Chen; Sumita Gokhale; Aditi Hazra; Donna Spiegelman; Edward L Giovannucci; Rudolf Jaenisch; Charles S Fuchs; Shuji Ogino Journal: Clin Cancer Res Date: 2009-05-26 Impact factor: 12.531
Authors: Ashraf E K Ibrahim; Mark J Arends; Ana-Luisa Silva; Andrew H Wyllie; Liliana Greger; Yoko Ito; Sarah L Vowler; Tim H-M Huang; Simon Tavaré; Adele Murrell; James D Brenton Journal: Gut Date: 2010-11-10 Impact factor: 23.059