title: New insights into the lymphovascular microanatomy of the colon and the risk of metastases in pT1 colorectal cancer obtained with quantitative methods and three-dimensional digital reconstruction.
abstract: OBJECTIVE
  UK faecal occult blood test screening has tripled the proportion of pT1 colorectal cancers. The risk of metastasis is predicted by depth of invasion, suggesting that access to deep lymphovascular vessels is important. The aim of this study was to quantify the distribution and size of the submucosal vasculature, and generate a novel three-dimensional (3D) model to validate the findings.
  
  
  RESULTS
  Thirty samples of normal large bowel wall were immunostained with CD31, a vascular endothelium marker, to identify blood vessels, which were quantified and digitally analysed for their number, circumference, area and diameter in the deep mucosa and submucosa (Sm1, Sm2, and Sm3). The model required serial sections, a double immunostain (using CD31 and D2-40), and 3D reconstruction. Significant differences were shown between submucosal layers in the number, circumference and area of vessels (P < 0.001). Blood vessels were most numerous in the mucosa (11.79 vessels/0.2 mm(2)) but smaller [median area of 247 μm(2) , interquartile range (IQR) 162-373 μm(2)] than in Sm2, where they were fewer in number (6.92 vessels/0.2 mm(2)) but considerably larger (2086 μm(2), IQR 1007-4784 μm(2)). The 3D model generated novel observations on lymphovascular structures.
  
  
  CONCLUSIONS
  The number and size of blood vessels do not increase with depth of submucosa, as hypothesized. The distribution of vessels suggests that we should investigate the area or volume of submucosal invasion rather than the depth.
authors.affiliation: Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, St James's University Hospital, Leeds, UK.|Leeds Teaching Hospitals Trust, Leeds, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Brown
authors.affiliation: Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, St James's University Hospital, Leeds, UK.|Leeds Teaching Hospitals Trust, Leeds, UK.|Translational Anaesthetic and Surgical Science, Leeds Institute of Biological and Clinical Sciences, St James's University Hospital, Leeds, UK.
authors.forename: Eu-Wing
authors.initials: EW
authors.lastname: Toh
authors.affiliation: Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, St James's University Hospital, Leeds, UK.|Leeds Teaching Hospitals Trust, Leeds, UK.|Translational Anaesthetic and Surgical Science, Leeds Institute of Biological and Clinical Sciences, St James's University Hospital, Leeds, UK.|Nottingham University Hospitals, Nottingham, UK.
authors.forename: Katherine J E
authors.initials: KJ
authors.lastname: Smith
authors.affiliation: Section of Molecular Gastroenterology, Leeds Institute of Biological and Clinical Sciences, St James's University Hospital, Leeds, UK.
authors.forename: Pamela
authors.initials: P
authors.lastname: Jones
authors.affiliation: Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, St James's University Hospital, Leeds, UK.|Leeds Teaching Hospitals Trust, Leeds, UK.
authors.forename: Darren
authors.initials: D
authors.lastname: Treanor
authors.affiliation: School of Computing, University of Leeds, Leeds, UK.
authors.forename: Derek
authors.initials: D
authors.lastname: Magee
authors.affiliation: Leeds Teaching Hospitals Trust, Leeds, UK.|Translational Anaesthetic and Surgical Science, Leeds Institute of Biological and Clinical Sciences, St James's University Hospital, Leeds, UK.
authors.forename: Dermot
authors.initials: D
authors.lastname: Burke
authors.affiliation: Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, St James's University Hospital, Leeds, UK.|Leeds Teaching Hospitals Trust, Leeds, UK.
authors.forename: Phil
authors.initials: P
authors.lastname: Quirke
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000473:pathology*; D003198:Computer Simulation; D055088:Early Detection of Cancer / Q000379:methods; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D007413:Intestinal Mucosa / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D019408:Platelet Endothelial Cell Adhesion Molecule-1
keywords: CD31; colorectal cancer; microvessel anatomy; submucosal plexus