Expression of epithelial to mesenchymal transition-related markers in lymph node metastases as a surrogate for primary tumor metastatic potential in breast cancer

Journal of Translational Medicine

Research

Barbara Seroczyńska¹  Jarosław Skokowski²  Marzena Wełnicka-Jaśkiewicz³  Jolanta Szade⁴  Wojciech Biernat⁴  Janusz Jaśkiewicz⁵  Anna J Żaczek⁶  Tomasz Ahrends⁶  Aleksandra Markiewicz⁷ 

[1] Bank of Frozen Tissues and Genetic Specimen, Medical University of Gdańsk, Dębinki 1, 80-211, Gdańsk, Poland;Bank of Frozen Tissues and Genetic Specimen, Medical University of Gdańsk, Dębinki 1, 80-211, Gdańsk, Poland;Department of Surgical Oncology, Medical University of Gdańsk, Smoluchowskiego 17, 80-214, Gdańsk, Poland;Department of Oncology and Radiotherapy, Medical University of Gdańsk, Dębinki 7, 80-211, Gdańsk, Poland;Department of Pathomorphology, Medical University of Gdańsk, Smoluchowskiego 17, 80-214, Gdańsk, Poland;Department of Surgical Oncology, Medical University of Gdańsk, Smoluchowskiego 17, 80-214, Gdańsk, Poland;Laboratory of Cell Biology, Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Dębinki 1, 80-211, Gdańsk, Poland;Laboratory of Cell Biology, Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Dębinki 1, 80-211, Gdańsk, Poland;Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland;

关键词: Breast cancer;    Primary tumor;    Lymph node metastasis;    Gene expression;    Immunohistochemistry;    Biomarkers;    Epithelial-mesenchymal transition;   

DOI  :  10.1186/1479-5876-10-226

 received in 2012-08-03, accepted in 2012-11-14,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundBreast cancers are phenotypically and genotypically heterogeneous tumors containing multiple cancer cell populations with various metastatic potential. Aggressive tumor cell subpopulations might more easily be captured in lymph nodes metastases (LNM) than in primary tumors (PT). We evaluated mRNA and protein levels of master EMT regulators: TWIST1, SNAIL and SLUG, protein levels of EMT-related markers: E-cadherin, vimentin, and expression of classical breast cancer receptors: HER2, ER and PgR in PT and corresponding LNM. The results were correlated with clinicopathological data and patients outcomes.MethodsFormalin-fixed paraffin-embedded samples from PT and matched LNM from 42 stage II-III breast cancer patients were examined. Expression of TWIST1, SNAIL and SLUG was measured by reverse-transcription quantitative PCR. Protein expression was examined by immunohistochemistry on tissue microarrays. Kaplan-Meier curves for disease-free survival (DFS) and overall survival (OS) were compared using F-Cox test. Hazard ratios (HRs) with 95% confidence intervals (95% CI) were computed using Cox regression analysis.ResultsOn average, mRNA expression of TWIST1, SNAIL and SLUG was significantly higher in LNM compared to PT (P < 0.00001 for all). Gene and protein levels of TWIST1, SNAIL and SLUG were highly discordant between PT and matched LNM. Increased mRNA expression of TWIST1 and SNAIL in LNM was associated with shorter OS (P = 0.04 and P = 0.02, respectively) and DFS (P = 0.02 and P = 0.01, respectively), whereas their expression in PT had no prognostic impact. Negative-to-positive switch of SNAIL protein correlated with decreased OS and DFS (HR = 4.6; 1.1-18.7; P = 0.03 and HR = 3.8; 1.0-48.7; P = 0.05, respectively).ConclusionsLNM are enriched in cells with more aggressive phenotype, marked by elevated levels of EMT regulators. High expression of TWIST1 and SNAIL in LNM, as well as negative-to-positive conversion of SNAIL confer worse prognosis, confirming the correlation of EMT with aggressive disease behavior. Thus, molecular profiling of LNM may be used as surrogate marker for aggressiveness and metastatic potential of PT.

【 授权许可】

Unknown   
© Markiewicz et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.