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Kristian Pietras

Kristian Pietras

Research team manager

Kristian Pietras

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

Author

  • Sara Jansson
  • Kristina Aaltonen
  • Pär Ola Bendahl
  • Anna Karin Falck
  • Maria Karlsson
  • Kristian Pietras
  • Lisa Rydén

Summary, in English

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.

Department/s

  • The Liquid Biopsy and Tumor Progression in Breast Cancer
  • Breastcancer-genetics
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
  • Personalized Breast Cancer Treatment
  • Division of Translational Cancer Research
  • Department of Laboratory Medicine
  • Breast Cancer Surgery
  • Surgery (Lund)

Publishing year

2018-06-01

Language

English

Pages

231-241

Publication/Series

Breast Cancer Research and Treatment

Volume

169

Issue

2

Document type

Journal article

Publisher

Springer

Topic

  • Cancer and Oncology

Keywords

  • Breast cancer
  • Platelet-derived growth factor receptor
  • Platelet-derived growth factor-CC
  • Targeted therapy
  • Triple-negative breast cancer
  • Tyrosine kinase receptor

Status

Published

Research group

  • The Liquid Biopsy and Tumor Progression in Breast Cancer
  • Personalized Breast Cancer Treatment
  • Breast Cancer Surgery

ISBN/ISSN/Other

  • ISSN: 0167-6806