engleski

Markers of epithelial-mesenchymal transition in brain metastases from lung cancer

Introduction: Autopsy studies indicated that the central nervous system (CNS) metastases occur in about 25% of patients who die of cancer. Still, the molecular basis for the metastasize of primary tumors to the brain is largely unknown. Recent studies have shown that epithelial-mesenchymal transition (EMT) could be involved in invasiveness of different tumor types. In this pilot study, we investigated TWIST and β-catenin in a set of collected brain metastases. Both proteins are involved in EMT, where TWIST acts as a transcriptional repressor of E-cadherin, while β- catenin plays role in Wnt signaling - evolutionarily conserved pathway related to carcinogenesis. Methods: TWIST and β-catenin protein expression and localization were investigated in 15 brain metastases samples originating from primary lung carcinomas. To assess and localize expression of proteins, we used DAB-labeled immunohistochemical reaction by an activity of streptavidin-horseradish peroxidase/DAB (EnVisionTM, Dako REALTM) and specific monoclonal antibodies for β-catenin and TWIST on paraffin-embedded metastases sections. Reaction staining was evaluated semi- quantitatively by three independent observers. Results: Our results showed that both proteins were upregulated in brain metastases. We demonstrated that strong nuclear immunostaining of TWIST was present in 53%, moderate in 20% and weak in 7% of investigated samples. Furthermore, β- catenin was up-regulated in 56% of brain metastases and transferred to the nucleus in 36% of them. Discussion: The reported improvement in overall survival of patients with CNS metastases may be linked to its biologic spectrum which is unfortunately wide and heterogenic. The secondary tumor establishment differs depending on the primary site and according to the genetic profile. Therefore, our results indicate that these two molecules are involved in the metastatic process to the brain. Conclusion: Our preliminary findings indicate involvement of TWIST and β-catenin in brain metastases from primary lung cancer. However, experiments and statistical analyses should be performed on a higher number of cases. Nevertheless, our findings could be useful as potential biomarkers of metastatic progression.

β-catenin ; TWIST ; Wnt ; epithelial-mesenchymal transition ; brain metastasis

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