Expression of epithelial-mesenchymal transition-related markers and phenotypes during breast cancer progression
Autor: | Charlotte Jørgensen, Carina Forsare, Anna Karin Falck, Kristina Lövgren, Mårten Fernö, Pär-Ola Bendahl, Kristina Aaltonen, Lisa Rydén |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Oncology Cancer Research Receptor ErbB-2 Vimentin Breast cancer 0302 clinical medicine Recurrence Prospective Studies Lymph node biology Hazard ratio Middle Aged Cadherins Prognosis Clinical Trial Tumor progression Primary tumor Survival Rate Phenotype medicine.anatomical_structure Receptors Estrogen 030220 oncology & carcinogenesis Disease Progression Immunohistochemistry Female Receptors Progesterone medicine.medical_specialty Epithelial-Mesenchymal Transition Breast Neoplasms 03 medical and health sciences EMT phenotypes Antigens CD Internal medicine Biomarkers Tumor medicine Humans Epithelial–mesenchymal transition business.industry medicine.disease 030104 developmental biology biology.protein Neoplasm Recurrence Local business Follow-Up Studies |
Zdroj: | Breast Cancer Research and Treatment |
ISSN: | 1573-7217 0167-6806 |
Popis: | Purpose The study aimed to investigate expression of epithelial-to-mesenchymal transition (EMT)-related proteins and phenotypes during breast cancer progression and to relate this to patient outcome. Methods Protein expression patterns of E-cadherin, N-cadherin, twist, and vimentin were examined by immunohistochemistry on formalin-fixed paraffin-embedded samples from primary tumors (PTs) (n = 419), synchronous lymph node metastases (LNMs) (n = 131) and recurrences (n = 34) from patients included in an observational prospective primary breast cancer study. Markers were evaluated individually and combined as defined EMT phenotypes (epithelial, mesenchymal, partial EMT, and negative). EMT profiles were compared between matched tumor progression stages, and related to clinicopathological data and distant recurrence-free interval (DRFi). Results N-cadherin-positivity, vimentin-positivity, mesenchymal and partial EMT phenotypes were associated with more aggressive tumor characteristics such as triple-negative subtype. Single EMT markers and phenotype discordance rates between paired tumor samples were observed in the range of 2–35%. Non-epithelial phenotypes were more frequently identified in recurrences compared to PTs, however, no skewness of expression or phenotype was detected between PTs and matched LNMs or between PTs and matched recurrences (Exact McNemar test). Interestingly, patients with a twist positive PT had shorter DRFi, compared to patients with a twist negative PT (hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.2–5.1, P = 0.02). Essentially, the same effect was seen in multivariable analysis (HR 2.5, 95% CI 0.97–6.6, P = 0.06). Conclusion The epithelial phenotype was indicated to be lost between PTs and recurrences as a reflection of tumor progression. Twist status of the PT was related to long-term prognosis warranting further investigation in larger cohorts. |
Databáze: | OpenAIRE |
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