[Frontiers in Bioscience E3, 616-624, January 1, 2011]

Molecular alterations of E-cadherin and beta-catenin in brain metastases

Martina Zeljko1 , Nives Pecina-Slaus1,2 , Tamara Nikuseva Martic1,2 , Vesna Kusec3, Vili Beros4, Davor Tomas5

1Laboratory of Neuro-oncology, Croatian Institute for Brain Research, School of Medicine University of Zagreb, Salata 12, HR-10000 Zagreb, Croatia, 2Department of Biology, School of Medicine, University of Zagreb, Salata 3, HR-10000 Zagreb, Croatia,3 Clinical Institute of Laboratory Diagnosis, Clinical Hospital Centre Zagreb, Kispaticeva 12, 10 000 Zagreb, Croatia, 4Department of Neurosurgery, University Hospital, Sisters of Charity, Vinogradska 29, 10000 Zagreb, Croatia, 5 Ljudevit Jurak Department of Pathology, University Hospital, Sisters of Charity, Vinogradska 29, 10000 Zagreb, Croatia

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and Methods
3.1. Tumor specimen
3.3. Polymerase chain reaction
3.2. DNA extraction
3.4. Loss of heterozygosity, replication error
3.5. Heteroduplex analysis
3.6. Immunohistochemistry
3.7. Image analysis
3.8. Statistical analysis
4. Results
5. Discussion
6. Acknowledgement
7. References

1. ABSTRACT

The molecular mechanisms and candidate genes involved in metastasis to the brain need elucidation. In the present study brain metastases were analyzed regarding changes of E-cadherin (CDH1) and beta-catenin (CTNNB1). Loss of heterozygosity (LOH) of the CDH1 gene was detected in 42.2% of samples. The highest frequency of LOHs was observed in metastases from primary sites of lung adenocarcinoma and small cell lung cancer. Metastases from breast and colon demonstrated changes in 55.6% and 50% of cases. Downregulation of E-cadherin protein was observed in 83% of samples. Only 21.1% of samples with E-cadherin LOH had beta-catenin located in the nucleus. Image analysis showed that the quantities of E-cadherin and beta-catenin were significantly positively correlated (P = 0.008). Changes of E-cadherin were frequent in brain metastases that we investigated. Lack of mutations of beta-catenin, the fact that it was not frequently found in the nucleus and the positive correlation between the two proteins may suggest that the break-up of adherens junctions, and not the activation of wnt signaling, is responsible for metastasis formation.