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Tumour cell invasion and metastasis are the processes which kill most cancer patients. Tumour cells with the greatest invasive and metastatic capacity may be those with the highest number of genetic aberrations. The present study has analysed the expression of several tumour-related proteins in both primary tumours and metastatic lesions from 34 breast cancer patients. Protein expression of p53, bcl-2, p21, cyclin D1, E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin was investigated by immunohistochemistry (IHC) using monoclonal antibodies. Metastatic tissue showed a different expression profile from the primary tumour in most patients. The most significant finding was the re-expression of E-cadherin, alpha-catenin, and beta-catenin, and increased down-regulation of gamma-catenin, in metastatic lesions. These results demonstrate that tumour cells, when released from the primary site and after regrowth elsewhere, are capable of re-expression of adhesion molecules. gamma-catenin may play a different role in metastatic lesions than in primary tumours, since it is selectively down-regulated in tumour tissue at the metastatic site.

In the metastatic process, various cell-cell adhesion molecules seem to play an important role. E-cadherin, a transmembrane protein with an extracellular and an intracellular domain, is one of the key players involved in cell-cell adhesion. The function of E-cadherin in preventing metastasis in tumour development is believed to be dependent on intracellular catenins. In a previous study, the expression of E-cadherin was examined in a series of human breast carcinomas. In that study, down-regulation of E-cadherin failed to correlate with lymph node and/or distant metastasis. In the present study, the expression of alpha-, beta-, and gamma-catenins has been examined in a subset of the same tumours in order to evaluate their possible role in breast cancer metastasis. Tumour tissues from 90 primary breast carcinomas were immunostained for alpha-, beta-, and gamma-catenins. Reduced or absent immunoreactivity in the tumour tissue was seen in 63 (70.0 per cent) for alpha-catenin, in 50 (55.6 per cent) for beta-catenin, and in 50 (55.6 per cent) for gamma-catenin. Reduced expression of each of the catenins alone failed to correlate to metastasis. However, when all of the four proteins (E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin) were analysed as one group, a significant association was seen between reduction in immunoreactivity of at least one of these four proteins and the presence of metastases. These results indicate that if one of these proteins is down-regulated, the function of the others in suppressing metastasis is altered. A significant association was seen between lobular invasive tumours and beta-catenin expression.

Alterations in the p53 protein are a common feature in most malignancies, including breast carcinomas. p53 protein alterations contribute to malignant transformation in several ways, through genomic instability and accumulation of additional genetic alterations in other genes, through alteration of the p53-dependent apoptotic pathway, and through downregulation of downstream effector proteins such as p21 (WAF1/CIP1), necessary for cell-cycle growth arrest. Cell-cycle arrest is needed to allow DNA repair after injury. This study examines the relationship between abnormalities in p53 protein and expression of p21 protein in 70 cases selected from a series of 212 sporadic human breast carcinomas. Immunohistochemistry (IHC) was used for detection of p53 and p21 protein expression. Constant denaturant gel electrophoresis (CDGE) was used for detection of mutations in exons 5-8 of the TP53 gene. A highly significant association was found between abnormalities in p53, scored as protein accumulation and/or mutations, and lack of p21 expression. p21 was also shown to be downregulated in samples without p53 alterations, indicating that other mechanisms are also involved in turning off this gene.