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

Aims 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 submuc...

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Veröffentlicht in:Histopathology 2015-08, Vol.67 (2), p.167-175
Hauptverfasser: Brown, Peter J, Toh, Eu-Wing, Smith, Katherine J E, Jones, Pamela, Treanor, Darren, Magee, Derek, Burke, Dermot, Quirke, Phil
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container_end_page 175
container_issue 2
container_start_page 167
container_title Histopathology
container_volume 67
creator Brown, Peter J
Toh, Eu-Wing
Smith, Katherine J E
Jones, Pamela
Treanor, Darren
Magee, Derek
Burke, Dermot
Quirke, Phil
description Aims 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. Methods and 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 
doi_str_mv 10.1111/his.12639
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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. Methods and 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 &lt; 0.001). Blood vessels were most numerous in the mucosa (11.79 vessels/0.2 mm2) but smaller [median area of 247 μm2, interquartile range (IQR) 162–373 μm2] than in Sm2, where they were fewer in number (6.92 vessels/0.2 mm2) but considerably larger (2086 μm2, IQR 1007–4784 μm2). 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.</description><identifier>ISSN: 0309-0167</identifier><identifier>EISSN: 1365-2559</identifier><identifier>DOI: 10.1111/his.12639</identifier><identifier>PMID: 25557923</identifier><identifier>CODEN: HISTDD</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Aged ; Biomarkers, Tumor - metabolism ; CD31 ; colorectal cancer ; Colorectal Neoplasms - blood supply ; Colorectal Neoplasms - pathology ; Computer Simulation ; Early Detection of Cancer - methods ; Endothelium, Vascular - metabolism ; Female ; Humans ; Image Processing, Computer-Assisted ; Imaging, Three-Dimensional ; Intestinal Mucosa - pathology ; Lymph Nodes - pathology ; Lymphatic Metastasis ; Male ; microvessel anatomy ; Middle Aged ; Neoplasm Invasiveness ; Neovascularization, Pathologic - metabolism ; Neovascularization, Pathologic - pathology ; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism ; Risk Factors ; submucosal plexus</subject><ispartof>Histopathology, 2015-08, Vol.67 (2), p.167-175</ispartof><rights>2015 John Wiley &amp; Sons Ltd</rights><rights>2015 John Wiley &amp; Sons Ltd.</rights><rights>Copyright © 2015 John Wiley &amp; Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4269-cdece918dd9eb49dbc456489e613ce0d50e0ac5257e8f906d1000737760956763</citedby><cites>FETCH-LOGICAL-c4269-cdece918dd9eb49dbc456489e613ce0d50e0ac5257e8f906d1000737760956763</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fhis.12639$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fhis.12639$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25557923$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brown, Peter J</creatorcontrib><creatorcontrib>Toh, Eu-Wing</creatorcontrib><creatorcontrib>Smith, Katherine J E</creatorcontrib><creatorcontrib>Jones, Pamela</creatorcontrib><creatorcontrib>Treanor, Darren</creatorcontrib><creatorcontrib>Magee, Derek</creatorcontrib><creatorcontrib>Burke, Dermot</creatorcontrib><creatorcontrib>Quirke, Phil</creatorcontrib><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</title><title>Histopathology</title><addtitle>Histopathology</addtitle><description>Aims 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. Methods and 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 &lt; 0.001). Blood vessels were most numerous in the mucosa (11.79 vessels/0.2 mm2) but smaller [median area of 247 μm2, interquartile range (IQR) 162–373 μm2] than in Sm2, where they were fewer in number (6.92 vessels/0.2 mm2) but considerably larger (2086 μm2, IQR 1007–4784 μm2). 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.</description><subject>Aged</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>CD31</subject><subject>colorectal cancer</subject><subject>Colorectal Neoplasms - blood supply</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Computer Simulation</subject><subject>Early Detection of Cancer - methods</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Image Processing, Computer-Assisted</subject><subject>Imaging, Three-Dimensional</subject><subject>Intestinal Mucosa - pathology</subject><subject>Lymph Nodes - pathology</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>microvessel anatomy</subject><subject>Middle Aged</subject><subject>Neoplasm Invasiveness</subject><subject>Neovascularization, Pathologic - metabolism</subject><subject>Neovascularization, Pathologic - pathology</subject><subject>Platelet Endothelial Cell Adhesion Molecule-1 - metabolism</subject><subject>Risk Factors</subject><subject>submucosal plexus</subject><issn>0309-0167</issn><issn>1365-2559</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kdFuFCEUhonR2LV64QsYEm_0YloYBlguTaPdJk1NbI2XhIWzHdqZYQtM1309n0xmd9sLE4EEyPn-Pxx-hN5TckLLOG19OqG1YOoFmlEmeFVzrl6iGWFEVYQKeYTepHRHCJWsrl-jo1LnUtVshv5cwQb7IfnbNqdyyAHnFnC37ddteDTJjp2JuPc2BjOYHPotDqsdYkMXBmwGt7tFn-6nSg_ZpLJgMsPrG7rjIthsOmzNYCHisMzGD-DwxucWP4xmyD6b7B9hkrfBpYNtBKic76E8LwxF7_ytn3yKXRhSjqPNpfAWvVqZLsG7w36Mfn77enO2qC6_n1-cfbmsbFMLVVkHFhSdO6dg2Si3tA0XzVyBoMwCcZwAMZbXXMJ8pYhwlBAimZSCKC6kYMfo0953HcPDCCnr3icLXWcGCGPSVChZ03kjWUE__oPehTGWFnaUIE2ZpFCf91T53JQirPQ6-t7EraZET8HqEqzeBVvYDwfHcdmDeyafkizA6R7Y-A62_3fSi4vrJ8tqr_Apw-9nhYn3WpS-uf51da6va04XzQ-mGfsLwgfAJA</recordid><startdate>201508</startdate><enddate>201508</enddate><creator>Brown, Peter J</creator><creator>Toh, Eu-Wing</creator><creator>Smith, Katherine J E</creator><creator>Jones, Pamela</creator><creator>Treanor, Darren</creator><creator>Magee, Derek</creator><creator>Burke, Dermot</creator><creator>Quirke, Phil</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201508</creationdate><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</title><author>Brown, Peter J ; Toh, Eu-Wing ; Smith, Katherine J E ; Jones, Pamela ; Treanor, Darren ; Magee, Derek ; Burke, Dermot ; Quirke, Phil</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4269-cdece918dd9eb49dbc456489e613ce0d50e0ac5257e8f906d1000737760956763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aged</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>CD31</topic><topic>colorectal cancer</topic><topic>Colorectal Neoplasms - blood supply</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Computer Simulation</topic><topic>Early Detection of Cancer - methods</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Female</topic><topic>Humans</topic><topic>Image Processing, Computer-Assisted</topic><topic>Imaging, Three-Dimensional</topic><topic>Intestinal Mucosa - pathology</topic><topic>Lymph Nodes - pathology</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>microvessel anatomy</topic><topic>Middle Aged</topic><topic>Neoplasm Invasiveness</topic><topic>Neovascularization, Pathologic - metabolism</topic><topic>Neovascularization, Pathologic - pathology</topic><topic>Platelet Endothelial Cell Adhesion Molecule-1 - metabolism</topic><topic>Risk Factors</topic><topic>submucosal plexus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brown, Peter J</creatorcontrib><creatorcontrib>Toh, Eu-Wing</creatorcontrib><creatorcontrib>Smith, Katherine J E</creatorcontrib><creatorcontrib>Jones, Pamela</creatorcontrib><creatorcontrib>Treanor, Darren</creatorcontrib><creatorcontrib>Magee, Derek</creatorcontrib><creatorcontrib>Burke, Dermot</creatorcontrib><creatorcontrib>Quirke, Phil</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Histopathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brown, Peter J</au><au>Toh, Eu-Wing</au><au>Smith, Katherine J E</au><au>Jones, Pamela</au><au>Treanor, Darren</au><au>Magee, Derek</au><au>Burke, Dermot</au><au>Quirke, Phil</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Histopathology</jtitle><addtitle>Histopathology</addtitle><date>2015-08</date><risdate>2015</risdate><volume>67</volume><issue>2</issue><spage>167</spage><epage>175</epage><pages>167-175</pages><issn>0309-0167</issn><eissn>1365-2559</eissn><coden>HISTDD</coden><abstract>Aims 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. Methods and 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 &lt; 0.001). Blood vessels were most numerous in the mucosa (11.79 vessels/0.2 mm2) but smaller [median area of 247 μm2, interquartile range (IQR) 162–373 μm2] than in Sm2, where they were fewer in number (6.92 vessels/0.2 mm2) but considerably larger (2086 μm2, IQR 1007–4784 μm2). 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.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>25557923</pmid><doi>10.1111/his.12639</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects Aged
Biomarkers, Tumor - metabolism
CD31
colorectal cancer
Colorectal Neoplasms - blood supply
Colorectal Neoplasms - pathology
Computer Simulation
Early Detection of Cancer - methods
Endothelium, Vascular - metabolism
Female
Humans
Image Processing, Computer-Assisted
Imaging, Three-Dimensional
Intestinal Mucosa - pathology
Lymph Nodes - pathology
Lymphatic Metastasis
Male
microvessel anatomy
Middle Aged
Neoplasm Invasiveness
Neovascularization, Pathologic - metabolism
Neovascularization, Pathologic - pathology
Platelet Endothelial Cell Adhesion Molecule-1 - metabolism
Risk Factors
submucosal plexus
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
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