Washington K, Chiappori A, Hamilton K, Shyr Y, Blanke C, Johnson D, Sawyers J, Beauchamp D
Department of Pathology, Vanderbilt University Medical Center, Vanderbilt Cancer Center, Nashville, Tennessee 37232-2561, USA.
Mod Pathol. 1998 Sep;11(9):805-13.
Loss of expression and function of the E-cadherin/catenin membrane complex can result in loss of cell adhesion and contribute to invasive or metastatic potential in carcinomas. The aim of this study was to examine the expression of alpha- and beta-catenin and E-cadherin in Barrett's esophagus with and without dysplasia and in esophageal adenocarcinomas and to identify any relationship with tumor growth pattern and clinical outcome. Immunoperoxidase staining for alpha- and beta-catenin and E-cadherin was performed on specimens of Barrett's esophagus with and without dysplasia and on 54 esophageal adenocarcinoma specimens. Membranous staining for all of the components was seen in normal gastric and esophageal mucosa. Abnormal expression of beta-catenin, alpha-catenin, and E-cadherin was significantly associated with higher degrees of dysplasia in Barrett's esophagus. Fourteen of 16 cases of high grade dysplasia and 7 of 7 cases of intramucosal carcinoma showed abnormal expression of beta-catenin, compared with 3 of 6 cases indefinite for dysplasia and 11 of 17 cases with low grade dysplasia (P = 0.022). Similar results were seen for expression of alpha-catenin (P < .01) and E-cadherin (P = .049). In esophageal adenocarcinomas, preserved expression of these proteins occurred more frequently in well-differentiated tumors; abnormal expression was more common in diffusely infiltrative poorly differentiated tumors that did not form glands. Focal nuclear staining for beta-catenin was present in two high-grade dysplasias, two intramucosal carcinomas, and five adenocarcinomas. No survival advantage was demonstrated for patients whose tumors retained expression of these cell adhesion components. In conclusion, abnormal expression of the E-cadherin/catenin membrane complex is common in esophageal adenocarcinoma and occurs early in the dysplasia/carcinoma sequence in Barrett's esophagus, indicating that disturbances in this cell adhesion complex might be important in tumorigenesis and tumor progression in this disorder.
E-钙黏蛋白/连环蛋白膜复合物表达及功能丧失可导致细胞黏附丧失，并促使癌具有侵袭性或转移潜能。本研究旨在检测伴有和不伴有发育异常的巴雷特食管以及食管腺癌中α-连环蛋白、β-连环蛋白和E-钙黏蛋白的表达情况，并确定其与肿瘤生长模式及临床结局之间的关系。对伴有和不伴有发育异常的巴雷特食管标本以及54例食管腺癌标本进行了α-连环蛋白、β-连环蛋白和E-钙黏蛋白的免疫过氧化物酶染色。在正常胃和食管黏膜中可见所有成分的膜染色。β-连环蛋白、α-连环蛋白和E-钙黏蛋白的异常表达与巴雷特食管更高程度的发育异常显著相关。16例高级别发育异常病例中有14例以及7例黏膜内癌病例中有7例显示β-连环蛋白异常表达，相比之下，6例发育异常不明确病例中有3例以及17例低级别发育异常病例中有11例出现异常表达（P = 0.022）。α-连环蛋白表达（P <.01）和E-钙黏蛋白表达（P = 0.049）也有类似结果。在食管腺癌中，这些蛋白的保留表达在高分化肿瘤中更常见；异常表达在未形成腺体的弥漫浸润性低分化肿瘤中更常见。在2例高级别发育异常、2例黏膜内癌和5例腺癌中可见β-连环蛋白的局灶性核染色。肿瘤保留这些细胞黏附成分表达的患者未显示出生存优势。总之，E-钙黏蛋白/连环蛋白膜复合物的异常表达在食管腺癌中很常见，且在巴雷特食管的发育异常/癌序列中早期出现，表明该细胞黏附复合物的紊乱可能在这种疾病的肿瘤发生和肿瘤进展中起重要作用。
