Valizadeh A, Karayiannakis A J, el-Hariry I, Kmiot W, Pignatelli M
Department of Histopathology, Royal Postgraduate Medical School, London, United Kingdom.
Am J Pathol. 1997 Jun;150(6):1977-84.
E-cadherin and its associated cytoplasmic proteins alpha-, beta-, and gamma-catenin and p120 protein play a crucial role in the maintenance of normal tissue architecture. Perturbation in any of these molecules results in loss of intercellular adhesion and cell transformation. In this study, we have used immunohistochemistry to localize E-cadherin, alpha-, beta-, and gamma-catenin, and p120 in paraffin-embedded tissues from 60 patients with colonic polyps. Specimens consisted of 20 samples each from hyperplastic, inflammatory, and sporadic adenomatous polyps. Ten histologically normal colonic samples were also studied. Normal colonic epithelial cells showed strong E-cadherin/ catenin/p120 immunostaining at the cell-cell junction. In 65% (13/20) of adenomatous polyps, beta-catenin showed abnormal nuclear localization with increased expression and loss of membranous staining compared with the adjacent normal mucosa. In two cases (10%), gamma-catenin was seen in the nuclei. Heterogeneous p120 immunoreactivity was observed in four cases (20%), of which two also showed beta-catenin nuclear localization. Preserved membranous alpha-catenin staining was seen in all cases. E-cadherin was down-regulated in 6 of 20 (30%) adenomas with loss of cell surface staining in 3 cases. All hyperplastic and 40% (8/20) of inflammatory polyps showed weak E-cadherin expression on the surface epithelium. Similar changes in p120 expression were seen in all hyperplastic and 20% (4/20) of inflammatory polyps. There were no concomitant changes in alpha-, beta-, or gamma-catenin expression. These results indicate that changes in catenin expression and cellular localization occur early in dysplastic colonic lesions.
E-钙黏蛋白及其相关的细胞质蛋白α-、β-和γ-连环蛋白以及p120蛋白在维持正常组织结构中起着至关重要的作用。这些分子中的任何一个发生紊乱都会导致细胞间黏附丧失和细胞转化。在本研究中,我们使用免疫组织化学方法在60例结肠息肉患者的石蜡包埋组织中定位E-钙黏蛋白、α-、β-和γ-连环蛋白以及p120。标本包括来自增生性、炎性和散发性腺瘤性息肉的各20个样本。还研究了10个组织学正常的结肠样本。正常结肠上皮细胞在细胞间连接处显示出强烈的E-钙黏蛋白/连环蛋白/p120免疫染色。在65%(13/20)的腺瘤性息肉中,与相邻正常黏膜相比,β-连环蛋白显示出异常的核定位,表达增加且膜染色缺失。在2例(10%)中可见γ-连环蛋白在细胞核中。在4例(20%)中观察到p120免疫反应性异质性,其中2例也显示β-连环蛋白核定位。所有病例中均可见α-连环蛋白膜染色保存。在20例腺瘤中的6例(30%)中E-钙黏蛋白下调,3例细胞表面染色缺失。所有增生性息肉和40%(8/20)的炎性息肉在表面上皮显示出E-钙黏蛋白表达较弱。在所有增生性息肉和20%(4/20)的炎性息肉中可见p120表达的类似变化。α-、β-或γ-连环蛋白表达没有伴随变化。这些结果表明连环蛋白表达和细胞定位的变化在发育异常的结肠病变中早期就会发生。