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

التفاصيل البيبلوغرافية
العنوان: Expression of epithelial to mesenchymal transition-related markers in lymph node metastases as a surrogate for primary tumor metastatic potential in breast cancer
المؤلفون: Markiewicz, Aleksandra, Ahrends, Tomasz, Wełnicka-Jaśkiewicz, Marzena, Seroczyńska, Barbara, Skokowski, Jarosław, Jaśkiewicz, Janusz, Szade, Jolanta, Biernat, Wojciech, Żaczek, Anna J
بيانات النشر: BioMed Central Ltd.
سنة النشر: 2012
المجموعة: BioMed Central
مصطلحات موضوعية: Breast cancer, Primary tumor, Lymph node metastasis, Gene expression, Immunohistochemistry, Biomarkers, Epithelial-mesenchymal transition
الوصف: Background Breast 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. Methods Formalin-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. Results On 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). Conclusions LNM 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 ...
نوع الوثيقة: report
اللغة: English
العلاقة: http://www.translational-medicine.com/content/10/1/226Test
الإتاحة: http://www.translational-medicine.com/content/10/1/226Test
حقوق: Copyright 2012 Markiewicz et al.; licensee BioMed Central Ltd.
رقم الانضمام: edsbas.C6956C64
قاعدة البيانات: BASE