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The PDGF pathway in breast cancer is linked to tumour aggressiveness, triple-negative subtype and early recurrence
PURPOSE: The platelet-derived growth factor (PDGF) signalling pathway is often dysregulated in cancer and PDGF-receptor expression has been linked to unfavourable prognostic factors in breast cancer (e.g. ER negativity, high Ki67 and high grade). This study aimed to evaluate the expression of PDGFRα...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer US
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945746/ https://www.ncbi.nlm.nih.gov/pubmed/29380207 http://dx.doi.org/10.1007/s10549-018-4664-7 |
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author | Jansson, Sara Aaltonen, Kristina Bendahl, Pär-Ola Falck, Anna-Karin Karlsson, Maria Pietras, Kristian Rydén, Lisa |
author_facet | Jansson, Sara Aaltonen, Kristina Bendahl, Pär-Ola Falck, Anna-Karin Karlsson, Maria Pietras, Kristian Rydén, Lisa |
author_sort | Jansson, Sara |
collection | PubMed |
description | PURPOSE: The platelet-derived growth factor (PDGF) signalling pathway is often dysregulated in cancer and PDGF-receptor expression has been linked to unfavourable prognostic factors in breast cancer (e.g. ER negativity, high Ki67 and high grade). This study aimed to evaluate the expression of PDGFRα, PDGFRβ and ligand PDGF-CC in breast cancer in relation to molecular subtypes and prognosis. METHODS: Protein expression of tumour and/or stromal cell PDGFRα, PDGFRβ and PDGF-CC was evaluated in primary tumours (N = 489), synchronous lymph node metastases (N = 135) and asynchronous recurrences (N = 39) using immunohistochemistry in a prospectively maintained cohort of primary breast cancer patients included during 1999–2003. Distant recurrence-free interval (DRFi) was the primary end-point. RESULTS: High expression of all investigated PDGF family members correlated to increasing Nottingham histopathological grade and high Ki67. Tumour cells displayed high expression of PDGFRα in 20%, and PDGF-CC in 21% of primary tumours, which correlated with the triple-negative subtype (TNBC). Patients with high PDGF-CC had inferior prognosis (P = 0.04) in terms of 5-year DRFi, whereas PDGFRα was up-regulated in lymph node metastasis and recurrences compared to primary tumours. High primary tumour PDGFRα was associated with increased risk of central nervous system (CNS) recurrence. CONCLUSIONS: High PDGFRα and PDGF-CC expression were linked to breast cancer with an aggressive biological phenotype, e.g. the TNBC subtype, and high PDGF-CC increased the risk of 5-year distant recurrence. Tumour cell PDGFRα was significantly up-regulated in lymph node metastases and asynchronous recurrences. Our findings support an active role of the PDGF signalling pathway in tumour progression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10549-018-4664-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5945746 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-59457462018-05-15 The PDGF pathway in breast cancer is linked to tumour aggressiveness, triple-negative subtype and early recurrence Jansson, Sara Aaltonen, Kristina Bendahl, Pär-Ola Falck, Anna-Karin Karlsson, Maria Pietras, Kristian Rydén, Lisa Breast Cancer Res Treat Preclinical Study PURPOSE: The platelet-derived growth factor (PDGF) signalling pathway is often dysregulated in cancer and PDGF-receptor expression has been linked to unfavourable prognostic factors in breast cancer (e.g. ER negativity, high Ki67 and high grade). This study aimed to evaluate the expression of PDGFRα, PDGFRβ and ligand PDGF-CC in breast cancer in relation to molecular subtypes and prognosis. METHODS: Protein expression of tumour and/or stromal cell PDGFRα, PDGFRβ and PDGF-CC was evaluated in primary tumours (N = 489), synchronous lymph node metastases (N = 135) and asynchronous recurrences (N = 39) using immunohistochemistry in a prospectively maintained cohort of primary breast cancer patients included during 1999–2003. Distant recurrence-free interval (DRFi) was the primary end-point. RESULTS: High expression of all investigated PDGF family members correlated to increasing Nottingham histopathological grade and high Ki67. Tumour cells displayed high expression of PDGFRα in 20%, and PDGF-CC in 21% of primary tumours, which correlated with the triple-negative subtype (TNBC). Patients with high PDGF-CC had inferior prognosis (P = 0.04) in terms of 5-year DRFi, whereas PDGFRα was up-regulated in lymph node metastasis and recurrences compared to primary tumours. High primary tumour PDGFRα was associated with increased risk of central nervous system (CNS) recurrence. CONCLUSIONS: High PDGFRα and PDGF-CC expression were linked to breast cancer with an aggressive biological phenotype, e.g. the TNBC subtype, and high PDGF-CC increased the risk of 5-year distant recurrence. Tumour cell PDGFRα was significantly up-regulated in lymph node metastases and asynchronous recurrences. Our findings support an active role of the PDGF signalling pathway in tumour progression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10549-018-4664-7) contains supplementary material, which is available to authorized users. Springer US 2018-01-29 2018 /pmc/articles/PMC5945746/ /pubmed/29380207 http://dx.doi.org/10.1007/s10549-018-4664-7 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Preclinical Study Jansson, Sara Aaltonen, Kristina Bendahl, Pär-Ola Falck, Anna-Karin Karlsson, Maria Pietras, Kristian Rydén, Lisa The PDGF pathway in breast cancer is linked to tumour aggressiveness, triple-negative subtype and early recurrence |
title | The PDGF pathway in breast cancer is linked to tumour aggressiveness, triple-negative subtype and early recurrence |
title_full | The PDGF pathway in breast cancer is linked to tumour aggressiveness, triple-negative subtype and early recurrence |
title_fullStr | The PDGF pathway in breast cancer is linked to tumour aggressiveness, triple-negative subtype and early recurrence |
title_full_unstemmed | The PDGF pathway in breast cancer is linked to tumour aggressiveness, triple-negative subtype and early recurrence |
title_short | The PDGF pathway in breast cancer is linked to tumour aggressiveness, triple-negative subtype and early recurrence |
title_sort | pdgf pathway in breast cancer is linked to tumour aggressiveness, triple-negative subtype and early recurrence |
topic | Preclinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945746/ https://www.ncbi.nlm.nih.gov/pubmed/29380207 http://dx.doi.org/10.1007/s10549-018-4664-7 |
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