Reduced intercellular adhesion is implicated in the development of metastasis. This study investigates the expression of intercellular adhesion molecules (E-cadherin, alpha-, beta-, gamma-catenin and claudin-7) and their influence on survival in primary breast carcinomas and corresponding axillary lymph node metastases (ALNM), and evaluates associations between them and with clinicopathological factors. The expression of adhesion molecules was analyzed immunohistochemically in tissues from 196 patients with primary invasive breast carcinomas and their nodal metastases (174 ductal and 22 lobular types). The expression was evaluated using semi-quantitative scoring of the intensity and proportion of immunoreactivity. All five adhesion proteins showed significantly reduced expression in primary ductal carcinomas with re-expression in ALNM (p<0.001). In uni- and multivariate analyses, the expression of E-cadherin in the primary tumours was a significant predictor of disease-free survival and distant disease-free survival. Thus, abnormal E-cadherin expression in the primary invasive breast carcinoma seems to be an independent prognostic biomarker in predicting a shorter survival in node-positive breast cancer patients. The results indicate that abnormal expression of the adhesion molecules in the primary tumours with re-expression in corresponding nodal metastases is a common event in breast ductal carcinomas and may play a central role in establishing metastasis.

Wide clinical criteria to select HNPCC kindreds, followed by immunohistochemistry of tumor material from one affected person in each family, had high sensitivity and specificity to predict MMR mutations.

Proliferative activity of tumour cells assessed by immunohistochemical Ki-67 expression is one of several prognostic indicators in breast cancer. The major objective of this study was to investigate the prognostic impact of Ki-67 proliferative activity in the axillary lymph node metastases and in the matched primary breast carcinoma from 194 patients. There was a statistically significant up-regulation of Ki-67 protein in the metastatic deposit compared to where the primary tumour was found (p = 0.001). A low Ki-67 index in both the primary and the metastatic tumours was a favorable prognostic factor. A high index in both primary and metastatic lesion and an up-regulation from a low index in the primary tumour to a high index in the metastatic deposit represented an unfavorable prognostic factor. Multivariate analysis showed that Ki-67 expression in the metastases was a superior independent prognostic factor of clinical outcomes compared to that in the primary tumours. Ki-67 expression in > or =10% of carcinoma cells in the primary tumours and > or =15% in the nodal metastases seems to be optimal cut-off levels. Ki-67 is of value as an independent prognostic factor in breast cancer.