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 PDGFR alpha, PDGFR beta and ligand PDGF-CC in breast cancer in relation to molecular subtypes and prognosis. Methods Protein expression of tumour and/or stromal cell PDGFR alpha, PDGFR beta 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 PDGFR alpha 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 PDGFR alpha was up-regulated in lymph node metastasis and recurrences compared to primary tumours. High primary tumour PDGFR alpha was associated with increased risk of central nervous system (CNS) recurrence. Conclusions High PDGFR alpha 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 PDGFR alpha 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.