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Expression of epithelial-mesenchymal transition-related markers and phenotypes during breast cancer progression

Jørgensen, Charlotte Levin Tykjær LU ; Forsare, Carina LU ; Bendahl, Pär Ola LU ; Falck, Anna Karin LU ; Fernö, Mårten LU ; Lövgren, Kristina LU ; Aaltonen, Kristina LU and Rydén, Lisa LU (2020) In Breast Cancer Research and Treatment 181(2). p.369-381
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Breast cancer, EMT phenotypes, Epithelial-mesenchymal transition, Primary tumor, Recurrence, Tumor progression
in
Breast Cancer Research and Treatment
volume
181
issue
2
pages
13 pages
publisher
Springer
external identifiers
  • scopus:85083505986
  • pmid:32300922
ISSN
0167-6806
DOI
10.1007/s10549-020-05627-0
language
English
LU publication?
yes
id
ad8fc6fa-247f-4201-9900-5f3f6a16b478
date added to LUP
2020-05-06 15:45:37
date last changed
2020-05-07 01:57:06
@article{ad8fc6fa-247f-4201-9900-5f3f6a16b478,
  abstract     = {<p>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.</p>},
  author       = {Jørgensen, Charlotte Levin Tykjær and Forsare, Carina and Bendahl, Pär Ola and Falck, Anna Karin and Fernö, Mårten and Lövgren, Kristina and Aaltonen, Kristina and Rydén, Lisa},
  issn         = {0167-6806},
  language     = {eng},
  month        = {04},
  number       = {2},
  pages        = {369--381},
  publisher    = {Springer},
  series       = {Breast Cancer Research and Treatment},
  title        = {Expression of epithelial-mesenchymal transition-related markers and phenotypes during breast cancer progression},
  url          = {http://dx.doi.org/10.1007/s10549-020-05627-0},
  doi          = {10.1007/s10549-020-05627-0},
  volume       = {181},
  year         = {2020},
}