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The PDGF pathway in breast cancer is linked to tumour aggressiveness, triple-negative subtype and early recurrence

Jansson, Sara LU ; Aaltonen, Kristina LU ; Bendahl, Pär Ola LU ; Falck, Anna Karin LU ; Karlsson, Maria ; Pietras, Kristian LU and Rydén, Lisa LU (2018) In Breast Cancer Research and Treatment 169(2). p.231-241
Abstract

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... (More)

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.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Breast cancer, Platelet-derived growth factor receptor, Platelet-derived growth factor-CC, Targeted therapy, Triple-negative breast cancer, Tyrosine kinase receptor
in
Breast Cancer Research and Treatment
volume
169
issue
2
pages
231 - 241
publisher
Springer
external identifiers
  • pmid:29380207
  • scopus:85041106916
ISSN
0167-6806
DOI
10.1007/s10549-018-4664-7
language
English
LU publication?
yes
id
f23c7ab4-73b8-46fa-bfad-cb8da427f1ad
date added to LUP
2019-05-31 13:52:45
date last changed
2020-10-20 05:05:42
@article{f23c7ab4-73b8-46fa-bfad-cb8da427f1ad,
  abstract     = {<p>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.</p>},
  author       = {Jansson, Sara and Aaltonen, Kristina and Bendahl, Pär Ola and Falck, Anna Karin and Karlsson, Maria and Pietras, Kristian and Rydén, Lisa},
  issn         = {0167-6806},
  language     = {eng},
  month        = {06},
  number       = {2},
  pages        = {231--241},
  publisher    = {Springer},
  series       = {Breast Cancer Research and Treatment},
  title        = {The PDGF pathway in breast cancer is linked to tumour aggressiveness, triple-negative subtype and early recurrence},
  url          = {http://dx.doi.org/10.1007/s10549-018-4664-7},
  doi          = {10.1007/s10549-018-4664-7},
  volume       = {169},
  year         = {2018},
}