Intestinal Differentiation in Metaplastic, Nongoblet Columnar Epithelium in the Esophagus
Intestinal Differentiation in Metaplastic, Nongoblet Columnar Epithelium in the Esophagus
复制标题
DOI：
10.1097/pas.0b013e31819f57e9
复制
发表时间：
2009-07-01
影响因子：
5.6
通讯作者：
Odze, Robert D.
中科院分区：
文献类型：
--
作者：
Hahn, Hejin P.;Blount, Patricia L.;Odze, Robert D.
Barrett食管（BE）的定义是在食管的内镜可识别区域内存在化生的食管柱状上皮和杯状细胞。然而，BE中的一些癌，或来自胃食管连接区的癌，在没有杯状细胞的粘膜内发展。然而，化生性食管非杯状柱状上皮的生物学特性、发病机制和恶性风险基本上是未知的。在这项研究中，对89例化生食管柱状上皮患者进行了免疫组化评估，以检测肠分化标志物，例如MUC 2、DAS-1、Villin和胃分化标志物CDX 2（MUC 5AC）以及细胞增殖标志物Ki 67。89例患者中，59例食管柱状上皮化生伴杯状细胞（BE），根据杯状细胞在隐窝中所占比例，BE又可分为低密度杯状细胞组和高密度杯状细胞组，30例食管柱状上皮化生不伴杯状细胞。作为对照，使用了19例年龄和性别匹配的无食管或胃病理的患者的胃活检。仅在所有患者组的非杯状柱状上皮中评价标志物的阳性率和Ki 67染色的位置。食管柱状上皮化生无杯状细胞的患者中，MMAC、MUC 2、DAS-1、Villin和CDX 2的阳性率分别为100%、0%、30%、17%和43%。17%的病例显示异常的表面Ki 67阳性。这些值显著高于胃对照，胃对照显示除MUC 5AC（100%）外所有标志物均不染色。在化生性食管柱状上皮伴杯状细胞（BE）患者中，除MUC 5AC外，所有标记物的染色率均显著增加。此外，与低密度杯状细胞相比，高密度杯状细胞的BE患者MUC 2和表面Ki 67染色均显著增加。在一项单独的分析中，与具有杯状细胞的粘膜区域相比，在没有杯状细胞的粘膜区域中评价了化生性食管非杯状上皮，来自粘膜中其他地方具有杯状细胞的患者（N = 59），在没有杯状细胞的区域中，在非杯状上皮中用任何标记物染色的病例百分比方面没有观察到显著差异，类似于无杯状细胞的化生食管上皮患者组（N = 30）。与上述相似，在所有情况下，肠标志物的表达在邻近杯状细胞的粘膜区域中增加。这项研究提供的证据表明，化生食管柱状上皮无杯状细胞显示肠分化的表型证据，并支持的理论，鳞状上皮细胞转化为非杯状柱状上皮杯状细胞化生前。需要进一步的前瞻性研究来评估化生性食管非杯状上皮的发病顺序、自然史和恶性风险。
Barrett esophagus (BE) is defined by the presence of metaplastic esophageal columnar epithelium with goblet cells within endoscopically recognizable areas of the esophagus. However, some carcinomas in BE, or from the gastroesophageal junction region, develop within mucosa devoid of goblet cells. However, the biologic properties, pathogenesis, and risk of malignancy of metaplastic, esophageal nongoblet columnar epithelium, is, essentially, unknown. In this study, 89 patients with metaplastic esophageal columnar epithelium were evaluated immunohistochemically for markers of intestinal differentiation, such as MUC2, DAS-1, Villin, and CDX2, a marker of gastric differentiation (MUC5AC), and Ki67, a marker of cell proliferation. Of the 89 patients, 59 had columnar metaplasia with goblet cells (BE), which were further separated into low-density goblet cell and high-density goblet cell groups based on the percentage of crypts with goblet cells, and 30 patients had columnar metaplasia of the esophagus without goblet cells. As controls, gastric biopsies from 19 age and sex matched patients without esophageal or gastric pathology were used. The rate of positivity of the markers and the location of Ki67 staining was evaluated only in non-goblet columnar epithelium from all patient groups. Patients with metaplastic esophageal columnar epithelium without goblet cells showed positivity for M MAC, MUC2, DAS-1, Villin, and CDX2 in 100%, 0%, 30%, 17%, and 43% of cases, respectively. 17% of cases showed aberrant surface Ki67 positivity. These values were significantly higher than gastric controls, which showed absence of staining for all markers except MUC5AC (100%). In patients with metaplastic esophageal columnar epithelium with goblet cells (BE) a significant increased rate of staining was observed for all markers, except MUC5AC. In addition, both MUC2 and surface Ki67 staining were significantly increased in BE patients with high-density goblet cells versus those with low-density goblet cells. In a separate analysis in which metaplastic esophageal nongoblet epithelium was evaluated in areas of mucosa devoid of goblet cells compared with areas of mucosa with goblet cells, from patients who had goblet cells elsewhere in the mucosa (N = 59), no significant differences were observed with regard to the percentage of cases that stained with any of the markers in the nongoblet epithelium in areas devoid of goblet cells, similar to the patient group with metaplastic esophageal epithelium without goblet cells (N = 30). Similar to above, in all cases, expression of intestinal markers increased in areas of mucosa adjacent to goblet cells. This study provides evidence that metaplastic esophageal columnar epithelium without goblet cells shows phenotypic evidence of intestinal differentiation and supports the theory that squamous epithelium converts initially to nongoblet columnar epithelium before goblet cell metaplasia. Further prospective studies are needed to evaluate the pathogenetic sequence, natural history, and risk of malignancy of metaplastic esophageal nongoblet epithelium.