Charlotte Levin Tykjær Jørgensen1, Carina Forsare2, Pär-Ola Bendahl2, Anna-Karin Falck3, Mårten Fernö2, Kristina Lövgren2, Kristina Aaltonen4, Lisa Rydén5,6. 1. Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Medicon Village, Building 404, 22381, Lund, Sweden. charlotte.levin_tykjaer_jorgensen@med.lu.se. 2. Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Medicon Village, Building 404, 22381, Lund, Sweden. 3. Department of Surgery, Helsingborg Hospital, Helsingborg, Sweden. 4. Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden. 5. Division of Surgery, Department of Clinical Sciences, Lund, Lund University, Lund, Sweden. 6. Department of Surgery, Skåne University Hospital, Lund, Sweden.
Abstract
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.
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.
Authors: Siti Norbaini Sabtu; S F Abdul Sani; L M Looi; S F Chiew; Dharini Pathmanathan; D A Bradley; Z Osman Journal: Sci Rep Date: 2021-02-05 Impact factor: 4.379
Authors: Mario Rosario D'Andrea; Vittore Cereda; Luigi Coppola; Guido Giordano; Andrea Remo; Elena De Santis Journal: Cancers (Basel) Date: 2021-11-25 Impact factor: 6.639