Hong M K, Laskin W B, Herman B E, Johnston M H, Vargo J J, Steinberg S M, Allegra C J, Johnston P G
National Cancer Institute-Navy Medical Oncology Branch, Bethesda, MD 20889-5105.
Cancer. 1995 Jan 15;75(2):423-9. doi: 10.1002/1097-0142(19950115)75:2<423::aid-cncr2820750202>3.0.co;2-5.
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.
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.
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.
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.
巴雷特食管是一种经组织学定义的食管癌前病变，其中正常的鳞状上皮被肠化生柱状上皮所取代。在从巴雷特食管发展为完全性癌的多步骤进程中，增殖加速可能预示或先于基因组不稳定，因此可能是恶性转化发病机制和/或预测中的一个重要因素。Ki-67是一种在增殖细胞（G1、S、G2和M期）中表达但在静止细胞（G0期）中不表达的核抗原。本研究旨在确定Ki-67表达是否与发育异常程度相关，以及Ki-67表达是否有助于鉴别有或无发育异常的患者。
使用免疫组织化学方法，用Ki-67抗体（MIB-1）分析43例患者的87份石蜡包埋食管活检标本中的Ki-67增殖分数。使用计算机化增殖指数程序（QNA v2.54，贝克顿·迪金森细胞成像系统公司，伊利诺伊州埃尔姆赫斯特），得出柱状上皮食管腔面、食管上段隐窝、下段隐窝及下方腺区的Ki-67评分。
在不同组织学类型的各区域中，Ki-67评分存在显著差异：正常胃黏膜（[NG]，n = 17）；无发育异常的巴雷特食管（[ND]，n = 17）；低级别发育异常（[LG]，n = 21）；高级别发育异常（[HG]，n = 14）；腺癌（[CA]，n = 5）。Ki-67表达模式与各组织学类型密切相关。各黏膜区域中Ki-67阳性核的百分比在统计学上可区分高级别与低级别发育异常（P < 0.001）。在高级别发育异常组织中，Ki-67阳性核主要见于表面上皮和上段隐窝区，而在低级别发育异常中，大多数Ki-67阳性核见于下段隐窝区。与伴有低级别发育异常组织的巴雷特食管相比，无发育异常的巴雷特食管各黏膜成分中Ki-67阳性核的数量也有显著差异（P < 0.001）。苏木精-伊红染色不确定为发育异常的染色模式分为几种不同模式（5例低级别发育异常、7例无发育异常、1例正常胃黏膜），而6例低级别发育异常活检标本的Ki-67表达模式与高级别发育异常更为一致。
Ki-67染色模式与巴雷特食管的组织学表现相关，可能是鉴别有或无发育异常患者的一个额外参数。
