BACKGROUND: Barrett's esophagus is a histologically defined premalignant lesion of the esophagus in which normal squamous epithelium is replaced by intestinalized columnar epithelium. In a multistep progression from Barrett's esophagus to fully developed carcinoma, accelerated proliferation may indicate or precede genomic instability and, therefore, may be an important factor in the pathogenesis and/or prediction of malignant transformation. Ki-67 is a nuclear antigen expressed in proliferating cells, (G1, S, G2, and M phases) but not in resting cells (G0 phase). This study was undertaken to determine if Ki-67 expression correlates with the degree of dysplasia and if Ki-67 expression can help to differentiate those patients with or without dysplasia. METHODS: The Ki-67 proliferation fraction in 87 paraffin embedded esophageal biopsies from 43 patients with the Ki-67 antibody (MIB-1) was analyzed using immunohistochemistry. Using a computerized proliferation index program (QNA v2.54, Becton Dickinson Cellular Imaging Systems, Inc., Elmhurst, IL), a Ki-67 score was derived for the luminal surface, upper esophageal crypt, lower crypt, and underlying glandular zone of the columnar-lined esophagus. RESULTS: Significant differences in Ki-67 scores were noted in each zone among different histologic categories: normal gastric ([NG] n = 17); Barrett's without dysplasia ([ND] n = 17); low grade dysplasia ([LG] n = 21); high grade dysplasia ([HG] n = 14); and adenocarcinoma ([CA] n = 5). The pattern of Ki-67 expression was associated strongly with each histologic category. The percentage of Ki-67 positive nuclei in each mucosal zone statistically separated high grade from low grade dysplasia (P < 0.001). In high grade dysplastic tissues, the Ki-67 positive nuclei were found predominantly on the surface epithelium and upper crypt zones, whereas in low grade dysplasia, the majority of Ki-67 positive nuclei were found in the lower crypt zone. The number of Ki-67 positive nuclei in each mucosal component also was significantly different in Barrett's esophagus without dysplasia when compared with Barrett's esophagus with low grade dysplastic tissues. (P < 0.001) Staining patterns of indefinite for dysplasia by H & E staining separated into several distinct patterns (five LG, seven ND, one NG) whereas six biopsies with low grade dysplasia had a Ki-67 expression pattern more consistent with that of high grade dysplasia. CONCLUSION: The Ki-67 staining pattern correlated with histologic findings in Barrett's esophagus and may represent an additional parameter for differentiating patients with or without dysplasia.
BACKGROUND: Barrett's esophagus is a histologically defined premalignant lesion of the esophagus in which normal squamous epithelium is replaced by intestinalized columnar epithelium. In a multistep progression from Barrett's esophagus to fully developed carcinoma, accelerated proliferation may indicate or precede genomic instability and, therefore, may be an important factor in the pathogenesis and/or prediction of malignant transformation. Ki-67 is a nuclear antigen expressed in proliferating cells, (G1, S, G2, and M phases) but not in resting cells (G0 phase). This study was undertaken to determine if Ki-67 expression correlates with the degree of dysplasia and if Ki-67 expression can help to differentiate those patients with or without dysplasia. METHODS: The Ki-67 proliferation fraction in 87 paraffin embedded esophageal biopsies from 43 patients with the Ki-67 antibody (MIB-1) was analyzed using immunohistochemistry. Using a computerized proliferation index program (QNA v2.54, Becton Dickinson Cellular Imaging Systems, Inc., Elmhurst, IL), a Ki-67 score was derived for the luminal surface, upper esophageal crypt, lower crypt, and underlying glandular zone of the columnar-lined esophagus. RESULTS: Significant differences in Ki-67 scores were noted in each zone among different histologic categories: normal gastric ([NG] n = 17); Barrett's without dysplasia ([ND] n = 17); low grade dysplasia ([LG] n = 21); high grade dysplasia ([HG] n = 14); and adenocarcinoma ([CA] n = 5). The pattern of Ki-67 expression was associated strongly with each histologic category. The percentage of Ki-67 positive nuclei in each mucosal zone statistically separated high grade from low grade dysplasia (P < 0.001). In high grade dysplastic tissues, the Ki-67 positive nuclei were found predominantly on the surface epithelium and upper crypt zones, whereas in low grade dysplasia, the majority of Ki-67 positive nuclei were found in the lower crypt zone. The number of Ki-67 positive nuclei in each mucosal component also was significantly different in Barrett's esophagus without dysplasia when compared with Barrett's esophagus with low grade dysplastic tissues. (P < 0.001) Staining patterns of indefinite for dysplasia by H & E staining separated into several distinct patterns (five LG, seven ND, one NG) whereas six biopsies with low grade dysplasia had a Ki-67 expression pattern more consistent with that of high grade dysplasia. CONCLUSION: The Ki-67 staining pattern correlated with histologic findings in Barrett's esophagus and may represent an additional parameter for differentiating patients with or without dysplasia.
Authors: M-A E J Ortner; B Ebert; E Hein; K Zumbusch; D Nolte; U Sukowski; J Weber-Eibel; B Fleige; M Dietel; M Stolte; G Oberhuber; R Porschen; B Klump; H Hörtnagl; H Lochs; H Rinneberg Journal: Gut Date: 2003-01 Impact factor: 23.059
Authors: Lisa A Lai; Rumen Kostadinov; Michael T Barrett; Daniel A Peiffer; Dimitry Pokholok; Robert Odze; Carissa A Sanchez; Carlo C Maley; Brian J Reid; Kevin L Gunderson; Peter S Rabinovitch Journal: Mol Cancer Res Date: 2010-07-20 Impact factor: 5.852
Authors: Stuart Jon Spechler; Rebecca C Fitzgerald; Ganapathy A Prasad; Kenneth K Wang Journal: Gastroenterology Date: 2010-01-18 Impact factor: 22.682