title: Intra-tumoural vessel area estimated by expression of epidermal growth factor-like domain 7 and microRNA-126 in primary tumours and metastases of patients with colorectal cancer: a descriptive study.
abstract: BACKGROUND
  Understanding the biological properties of potential drug targets are important. This is especially true for anti-angiogenic therapies in the search for potential biomarkers. The aim of the present descriptive study was to analyse the intra-tumoural expressions of epidermal growth factor-like domain 7 (EGFL7) and microRNA-126 (miRNA-126) in primary tumours from patients with stage II-IV colorectal cancer (CRC) and in paired samples of primary tumours, regional lymph node metastases and distant metastases.
  
  
  METHODS
  A total of 126 patients were included. Analyses were performed on resections of primary tumours, regional lymph node metastases, and large needle biopsies from distant metastases. EGFL7 was analysed by immunohistochemistry (IHC) and miRNA-126 by in situ hybridization (ISH). Both biomarkers were quantified by image guided analyses to determine the relative fraction estimates of vessel areas (VA).
  
  
  RESULTS
  The intra-tumoural EGFL7 VA was significantly higher in primary tumours from patients with recurrent disease than in patients without relapse in both stage II and III, p = 0.019 and p = 0.001, respectively. The EGFL7 VA was significantly higher and the miRNA-126 VA significantly lower in regional lymph node metastases compared to primary tumours, p = 0.01 and p < 10(-6), respectively. Furthermore, the miRNA-126 VA in liver metastases was significantly lower than in the primary tumours, p = 0.02.
  
  
  CONCLUSIONS
  The intra-tumoural expression of EGFL7 in early stages of CRC may influence the risk of post-surgical recurrence. Differential expression of miRNA-126 seems more pronounced in disseminated disease, which supports its role as a regulator in the metastatic process.
authors.affiliation: Department of Oncology, Vejle Hospital, part of Lillebaelt Hospital, Kabbeltoft 25, 7100, Vejle, Denmark. torben.hansen@rsyd.dk.|Institute of Regional Health Research, University of Southern Denmark, Region of Southern Denmark, Denmark. torben.hansen@rsyd.dk.
authors.forename: Torben Frøstrup
authors.initials: TF
authors.lastname: Hansen
authors.affiliation: Bioneer A/S, Hørsholm, Denmark. BSN@bioneer.dk.
authors.forename: Boye Schnack
authors.initials: BS
authors.lastname: Nielsen
authors.affiliation: Department of Oncology, Vejle Hospital, part of Lillebaelt Hospital, Kabbeltoft 25, 7100, Vejle, Denmark. anders.jakobsen@rsyd.dk.|Institute of Regional Health Research, University of Southern Denmark, Region of Southern Denmark, Denmark. anders.jakobsen@rsyd.dk.
authors.forename: Anders
authors.initials: A
authors.lastname: Jakobsen
authors.affiliation: Department of Clinical Pathology, Vejle Hospital, part of Lillebaelt Hospital, Vejle, Denmark. flemming.brandt.soerensen@rsyd.dk.|Institute of Regional Health Research, University of Southern Denmark, Region of Southern Denmark, Denmark. flemming.brandt.soerensen@rsyd.dk.
authors.forename: Flemming Brandt
authors.initials: FB
authors.lastname: Sørensen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002135:Calcium-Binding Proteins; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D066255:EGF Family of Proteins; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged
chemical_list: D002135:Calcium-Binding Proteins; D066255:EGF Family of Proteins; C527877:EGFL7 protein, human; D016228:Endothelial Growth Factors; C527111:MIRN126 microRNA, human; D035683:MicroRNAs