Journal Article

DKFZ-2017-00231

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Co-expression of MET and CD47 is a novel prognosticator for survival of luminal breast cancer patients.

Baccelli, I. (First author)DKFZ* ; Stenzinger, A. ; Vogel, V.DKFZ* ; Pfitzner, B. M. ; Klein, C.DKFZ* ; Wallwiener, M. ; Scharpff, M. ; Saini, M. ; Holland-Letz, T.DKFZ* ; Sinn, H.-P. ; Schneeweiss, A. ; Denkert, C.DKFZ* ; Weichert, W. ; Trumpp, A. (Last author)DKFZ*

2014
Impact Journals LLC [S.l.]

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Please use a persistent id in citations: doi:10.18632/oncotarget.2385

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.

Keyword(s): Antigens, CD47 ; Biomarkers, Tumor ; CD47 protein, human ; MET protein, human ; Proto-Oncogene Proteins c-met

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Contributing Institute(s):

1. Stammzellen und Krebs (A010)
2. Biostatistik (C060)
3. DKTK Heidelberg (L101)
4. DKTK Berlin (L201)

Research Program(s):

1. 311 - Signalling pathways, cell and tumor biology (POF3-311) (POF3-311)

Appears in the scientific report 2014

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Database coverage:
; BIOSIS Previews ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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