Expression of the E-cadherin-catenin cell adhesion complex in primary squamous cell carcinomas of the head and neck and their nodal metastases

Abstract

Expression of the E-cadherin-catenin cell adhesion complex in primary squamous cell carcinomas of the head and neck and their nodal metastases NA Andrews1l23, AS Jones1, TR Helliwell3 and AR Kinsella2Departments of 1Otorhinolaryngology, 2Surgery and 3Pathology, University of Liverpool, Liverpool, UK Summary 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 P-catenin generally paralleled that of E-cadherin, but in 12 cases there was strong membranous P-catenin expression in samples that exhibited predominantly cytoplasmic E-cadherin labelling. Expression of a-catenin was generally weak and did not correlate with the expression of either P-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.

E‐cadherin is a selective and strongly dominant prognostic factor in squamous cell carcinoma: A comparison of E‐cadherin with desmosomal components

“…Most importantly, in many of these studies, paraffin-embedded material was examined. For instance, Andrews et al 61 stated that none of the tumors had normal ecad expression.. Franchi et al 21 have used 20% of stained tumor cells as cutoff point for statistical analysis, which points to a generally much lower staining efficiency on paraffin sections as compared to frozen sections (our median staining score was 3.0 which corresponds to approximately 70% of normally stained tumor cells and the remainder showing intermediately reduced staining). Bankfalvi et al 23 and Rodrigo et al 30 reported ecad staining in normal squamous epithelium to be confined to basal and parabasal layers only.…”

Expression of E-cadherin, α-catenin, and β-catenin in the process of lymph node metastasis in oral squamous cell carcinoma

“…All sections were examined by three independent pathologists who were blinded to the patients' clinical information, using a slight modification of the scoring method described previously (Andrews et al, 1997), and the staining pattern was evaluated semiquantitatively by comparing the intensity and cellular localisation of immunostaining with those of the adjacent normal epithelium as an internal positive control. If immunoreaction was uniformly membraneous and strong, similar to that in the internal controls, the staining was defined as normal.…”

“…Changes or alteration in the function and expression of the cell to cell adhesion molecule, Ecadherin, a-catenin and b-catenin, have been postulated to be an early event in the multiple process of tumour metastasis and an important factor in tumour progression (Birchmeier et al, 1993;Ponta et al, 1994). A variety of studies regarding the relationship between the expression of E-cadherin, a-catenin, b-catenin and the existence of lymph node metastasis in human cancers have been performed and some authors found a significant correlation (Sato et al, 1999;Zheng et al, 1999), while others did not (Mattijssen et al, 1993;Andrews et al, 1997).…”

Correlation of β-catenin expresssion and metastasis in tongue squamous cell carcinoma

“…In particular, it has been suggested that the reduction of cell adhesion mediated by ß-catenin/ E-cadherin complexes is associated with the development and progression of squamous cell carcinomas of the head and neck 4 .…”