Brigham and Women's Hospital, Boston, MA 02115, USA.
Am J Surg Pathol. 2011 Jul;35(7):1007-13. doi: 10.1097/PAS.0b013e318218940d.
Currently, the American College of Gastroenterology requires identification of goblet cells in mucosal biopsies from the esophagus to diagnose Barrett esophagus (BE). Identification of goblet cells in mucosal biopsies is fraught with limitations such as sampling and interpretation error. One previous study by our group suggested that MUC2 expression in esophageal nongoblet columnar cells represents a late biochemical reaction in the conversion of mucinous columnar cells to goblet cells in BE. We conducted this study to evaluate the prevalence, sensitivity, and specificity of MUC2 positivity in nongoblet columnar epithelium for detection of goblet cells in the distal esophagus and gastroesophageal junction (GEJ) region. We also sought to identify associations between MUC2 positivity and clinical and endoscopic risk factors for BE. This analysis utilized mucosal biopsies of the distal esophagus or GEJ from 100 patients who participated in a community clinic-based study of patients with chronic gastroesophageal reflux disease evaluated prospectively in the western part of Washington state. We randomly selected 50 patients who had columnar epithelium with goblet cells, representing the study group and 50 patients without goblet cells, representing the comparison group. Immunohistochemistry for MUC2 was performed on samples in a blinded manner without knowledge of the clinical or endoscopic features of the patients. The presence of staining was noted in both goblet and nongoblet epithelium, both close to and distant from the mucosa with goblet cells, when the latter were present. All study patients showed MUC2 positivity in goblet cells. MUC2 was present in nongoblet columnar epithelium in 78% of study patients with goblet cells, but in only 4% of controls without goblet cells (P<0.0001) (sensitivity, 78%; specificity, 96% for goblet cell metaplasia). MUC2 was significantly more common in nongoblet columnar cells close to, rather than distant from, the mucosa with goblet cells (P<0.00001). Finally, MUC2 was significantly associated with endoscopic evidence of columnar metaplasia in the distal esophagus, and with known risk factors for BE, such as older age, white race, frequent heartburn, and elevated body mass index. We conclude that goblet cells likely develop from a field of MUC2-positive mucinous columnar cells, and as such, MUC2 represents a late event in the development of goblet cells. MUC2 staining in nongoblet columnar cells is a reasonably sensitive and highly specific marker for goblet cells in the distal esophagus and GEJ, and its presence is predictive of endoscopic columnar metaplasia of the esophagus, even in patients without goblet cells.
目前，美国胃肠病学会要求在食管黏膜活检中识别杯状细胞，以诊断 Barrett 食管 (BE)。在食管黏膜活检中识别杯状细胞存在采样和解释错误等局限性。我们小组的一项先前研究表明，食管非柱状细胞中的 MUC2 表达代表了 BE 中粘液柱状细胞向杯状细胞转化的晚期生化反应。我们进行这项研究是为了评估 MUC2 在非柱状上皮中的阳性率在检测远端食管和胃食管交界处 (GEJ) 区的杯状细胞中的患病率、敏感性和特异性。我们还试图确定 MUC2 阳性与 BE 的临床和内镜危险因素之间的关联。该分析利用了来自 100 名参与以社区为基础的慢性胃食管反流病患者前瞻性研究的患者的远端食管或 GEJ 的黏膜活检，这些患者在华盛顿州西部进行了评估。我们随机选择了 50 名具有杯状细胞的柱状上皮患者作为研究组，50 名无杯状细胞的患者作为对照组。对 MUC2 的免疫组织化学染色在盲法下进行，而不了解患者的临床或内镜特征。当存在杯状细胞时，在杯状和非杯状上皮中均观察到染色，无论是靠近还是远离具有杯状细胞的黏膜。所有研究患者的杯状细胞均显示 MUC2 阳性。在具有杯状细胞的研究患者中，78%的患者的非柱状上皮中有 MUC2，但在无杯状细胞的对照组中只有 4%（P<0.0001）（敏感性 78%；特异性 96%用于杯状细胞化生）。MUC2 在靠近而非远离具有杯状细胞的黏膜的非柱状细胞中更为常见（P<0.00001）。最后，MUC2 与远端食管的内镜柱状上皮化生证据以及 BE 的已知危险因素（如年龄较大、白种人、频繁烧心和体重指数升高）显著相关。我们得出结论，杯状细胞可能是从 MUC2 阳性粘液柱状细胞的区域发展而来的，因此 MUC2 代表了杯状细胞发育的晚期事件。非柱状细胞中的 MUC2 染色是远端食管和 GEJ 中杯状细胞的一种合理敏感和高度特异的标志物，其存在可预测食管的内镜柱状上皮化生，即使在没有杯状细胞的患者中也是如此。
