Andrews N A, Jones A S, Helliwell T R, Kinsella A R
Department of Otorhinolaryngology, University of Liverpool, UK.
Br J Cancer. 1997;75(10):1474-80. doi: 10.1038/bjc.1997.252.
Reductions in cell-cell adhesion and stromal and vascular invasion are essential steps in the progression from localized malignancy to metastatic disease. In this study, changes in the expression of the components of the E-cadherin-catenin cell adhesion complex have been investigated using immunohistochemical techniques in primary tumours and nodal metastases from 36 patients with squamous cell carcinoma of the head and neck. For 14 patients the corresponding primary and nodal metastases samples were available. None of the 51 samples showed normal E-cadherin expression when compared with either the adjacent normal squamous epithelium or with normal colonic epithelium that was used as positive control material. In 88% of primary tumours fewer than 50% of cells exhibited normal membranous E-cadherin expression. Loss of membranous E-cadherin expression was more extensive in poorly differentiated carcinomas while, in individual carcinomas, membranous E-cadherin expression was stronger in those parts of the neoplasm that expressed the differentiation marker involucrin. Expression of beta-catenin generally paralleled that of E-cadherin, but in 12 cases there was strong membranous beta-catenin expression in samples that exhibited predominantly cytoplasmic E-cadherin labelling. Expression of alpha-catenin was generally weak and did not correlate with the expression of either beta-catenin or E-cadherin. Marked intratumoral heterogeneity for protein expression was evident for all antibodies, and the abnormal expression of the catenins is a novel finding. E-cadherin is expressed more intensely in cells with greater squamous differentiation, but there was no correlation between the decreased expression of any of the adhesion molecules of the E-cadherin complex tested and local recurrence, metastasis or survival. The loss of expression of components of the E-cadherin complex is a common abnormality in squamous carcinomas and, while it may be permissive for metastasis, it does not appear to be the only determinant of this process.
细胞间黏附以及基质和血管侵袭的减少是从局限性恶性肿瘤进展为转移性疾病的关键步骤。在本研究中，利用免疫组织化学技术，对36例头颈部鳞状细胞癌患者的原发性肿瘤和淋巴结转移灶中E-钙黏蛋白-连环蛋白细胞黏附复合体各组分的表达变化进行了研究。对于14例患者，可获得相应的原发性肿瘤和淋巴结转移灶样本。与相邻正常鳞状上皮或用作阳性对照材料的正常结肠上皮相比，51个样本中均未显示出正常的E-钙黏蛋白表达。在88%的原发性肿瘤中，少于50%的细胞表现出正常的膜性E-钙黏蛋白表达。在低分化癌中，膜性E-钙黏蛋白表达的缺失更为广泛，而在个别癌中，肿瘤中表达分化标志物内披蛋白的部分，其膜性E-钙黏蛋白表达更强。β-连环蛋白的表达通常与E-钙黏蛋白的表达平行，但在12例样本中，β-连环蛋白呈强膜性表达，而这些样本中E-钙黏蛋白主要呈细胞质标记。α-连环蛋白的表达通常较弱，且与β-连环蛋白或E-钙黏蛋白的表达均无相关性。所有抗体均显示出明显的肿瘤内蛋白表达异质性，连环蛋白的异常表达是一个新发现。E-钙黏蛋白在具有更高鳞状分化的细胞中表达更强烈，但所检测的E-钙黏蛋白复合体的任何一种黏附分子表达降低与局部复发、转移或生存之间均无相关性。E-钙黏蛋白复合体各组分表达的缺失是鳞状细胞癌中的常见异常，虽然它可能为转移创造了条件，但似乎并不是这一过程的唯一决定因素。
