Co-expression of MET and CD47 is a novel prognosticator for survival of luminal-type breast cancer patients

Irène Baccelli, Albrecht Stenzinger, Vanessa Vogel, Berit Maria Pfitzner, Corinna Klein, Markus Wallwiener, Martina Scharpff, Massimo Saini, Tim Holland-Letz, Hans Peter Sinn, Andreas Schneeweiss, Carsten Denkert, Wilko Weichert, Andreas Trumpp

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Although luminal-type primary breast cancer can be efficiently treated, development of metastatic disease remains a significant clinical problem. We have previously shown that luminal-type circulating tumor cells (CTCs) co-expressing the tyrosine-kinase MET and CD47, a ligand involved in cancer cell evasion from macrophage scavenging, are able to initiate metastasis in xenografts. Here, we investigated the clinical relevance of MET-CD47 co-expression in 255 hormone receptor positive breast tumors by immunohistochemistry and found a 10.3-year mean overall-survival difference between MET-CD47 double-positive and double-negative patients (p<0.001). MET-CD47 co-expression defined a novel independent prognosticator for overall-survival by multivariate analysis (Cox proportional hazards model: HR: 4.1, p<0.002) and CD47 expression alone or in combination with MET was strongly associated with lymph node metastasis. Furthermore, flow cytometric analysis of metastatic patient blood revealed consistent presence of MET+CD47+ CTCs (range 0.8 - 33.3% of CTCs) and their frequency was associated with increased metastatic spread. Finally, primary uncultured CTCs with high MET+CD47+ content showed an enhanced capacity to initiate metastasis in mice. Detection and targeting of MET and CD47 may thus provide a rational basis for risk stratification and treatment of patients with luminal-type breast cancer.

Original languageEnglish
Pages (from-to)8147-8160
Number of pages14
JournalOncotarget
Volume5
Issue number18
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • Biomarker
  • Breast cancer
  • CD47
  • Circulating tumor cells
  • MET
  • Metastasis
  • Metastasis-stem cell
  • Prognosis

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