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The angiogenic switch occurs at the adenoma stage of the adenoma-carcinoma sequence in colorectal cancer
  1. Carolyn A Staton (c.a.staton{at}sheffield.ac.uk)
  1. University of Sheffield, United Kingdom
    1. Andrew SA Chetwood (mda01asc{at}sheffield.ac.uk)
    1. University of Sheffield, United Kingdom
      1. Iain C Cameron (iain.cameron{at}sth.nhs.uk)
      1. University of Sheffield, United Kingdom
        1. Simon S Cross (s.s.cross{at}sheffield.ac.uk)
        1. University of Sheffield, United Kingdom
          1. Nicola J Brown (n.j.brown{at}sheffield.ac.uk)
          1. University of Sheffield, United Kingdom
            1. Malcolm WR Reed (m.w.reed{at}shef.ac.uk)
            1. University of Sheffield, United Kingdom

              Abstract

              Objective: The aim of this study was to examine the relationship between tissue factor (TF), vascular endothelial growth factor (VEGF) and the onset of angiogenesis in the adenoma-carcinoma sequence (ACS), the stepwise process encompassing colorectal cancer (CRC) disease progression.

              Patients & Methods: 210 surgical specimens comprising the ACS were immunohistochemically stained for endothelial cells (CD31), VEGF and TF. Angiogenesis quantified using Chalkley grid analysis (MVD), and VEGF/TF expression were semi quantitavely graded and correlated with standard prognostic indicators including 5 year follow up. VEGF and TF were measured by ELISA in tumour specimens and normal mucosa from an additional 90 CRC patients.

              Results: There was a significant increase in MVD across the ACS (p<0.0005) with significant correlations with Dukes’ stage (p=0.01) and lymph node involvement (p=0.02). The greatest increase in MVD was related to the onset of dysplasia with an associated significant increase in VEGF expression (p<0.0005). There was a significant relationship between VEGF and TF expression in the initial phase of the ACS (k=0.44, p<0.005), although no correlation between VEGF or TF, and MVD, tumour size, Dukes' classification, lymph node involvement or survival was found.

              Conclusions: These findings are the first to suggest that the angiogenic switch occurs at the onset of dysplasia in the ACS and provide further evidence of the close association between VEGF and TF, in the early stages of CRC development.

              • angiogenesis
              • haemostasis
              • tissue factor
              • VEGF
              • colorectal cancer

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