First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours
Identifieur interne : 003C74 ( Pmc/Checkpoint ); précédent : 003C73; suivant : 003C75First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours
Auteurs : I. Van Der Auwera [Belgique] ; Y. Cao [Suède] ; J C Tille [Suède] ; M S Pepper [Afrique du Sud] ; D G Jackson [Royaume-Uni] ; S B Fox [Australie] ; A L Harris [Royaume-Uni] ; L Y Dirix [Belgique] ; P B Vermeulen [Belgique]Source :
- British Journal of Cancer [ 0007-0920 ] ; 2006.
Abstract
The lymphatic system is the primary pathway of metastasis for most human cancers. Recent research efforts in studying lymphangiogenesis have suggested the existence of a relationship between lymphatic vessel density and patient survival. However, current methodology of lymphangiogenesis quantification is still characterised by high intra- and interobserver variability. For the amount of lymphatic vessels in a tumour to be a clinically useful parameter, a reliable quantification technique needs to be developed. With this consensus report, we therefore would like to initiate discussion on the standardisation of the immunohistochemical method for lymphangiogenesis assessment.
Url:
DOI: 10.1038/sj.bjc.6603445
PubMed: 17117184
PubMed Central: 2360768
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours</title><author><name sortKey="Van Der Auwera, I" sort="Van Der Auwera, I" uniqKey="Van Der Auwera I" first="I" last="Van Der Auwera">I. Van Der Auwera</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Translational Cancer Research Group Antwerp, Laboratory of Pathology, University of Antwerp/University Hospital Antwerp, Edegem 2650, Belgium; Oncology Centre, General Hospital Sint-Augustinus</institution>, Wilrijk 2610,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cao, Y" sort="Cao, Y" uniqKey="Cao Y" first="Y" last="Cao">Y. Cao</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Laboratory of Angiogenesis Research, Microbiology and Tumor Biology Center, Karolinska Institutet</institution>, Stockholm 171 77,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Tille, J C" sort="Tille, J C" uniqKey="Tille J" first="J C" last="Tille">J C Tille</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Microbiology, Laboratory of Angiogenesis Research, Tumor and Cell Biology, Karolinska Institutet</institution>, Stockholm 171 77,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Pepper, M S" sort="Pepper, M S" uniqKey="Pepper M" first="M S" last="Pepper">M S Pepper</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>NetCare Molecular Medicine Institute, Unitas Hospital and Department of Immunology, Faculty of Health Sciences, University of Pretoria</institution>, Pretoria 0002,<country>South Africa</country></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jackson, D G" sort="Jackson, D G" uniqKey="Jackson D" first="D G" last="Jackson">D G Jackson</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital</institution>, Oxford OX3 9DS,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Fox, S B" sort="Fox, S B" uniqKey="Fox S" first="S B" last="Fox">S B Fox</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Department of Pathology, Peter MacCallum Cancer Centre</institution>, Victoria 8006,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Harris, A L" sort="Harris, A L" uniqKey="Harris A" first="A L" last="Harris">A L Harris</name><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Cancer Research UK Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital</institution>, Oxford OX3 9DS,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dirix, L Y" sort="Dirix, L Y" uniqKey="Dirix L" first="L Y" last="Dirix">L Y Dirix</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Translational Cancer Research Group Antwerp, Laboratory of Pathology, University of Antwerp/University Hospital Antwerp, Edegem 2650, Belgium; Oncology Centre, General Hospital Sint-Augustinus</institution>, Wilrijk 2610,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Vermeulen, P B" sort="Vermeulen, P B" uniqKey="Vermeulen P" first="P B" last="Vermeulen">P B Vermeulen</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Translational Cancer Research Group Antwerp, Laboratory of Pathology, University of Antwerp/University Hospital Antwerp, Edegem 2650, Belgium; Oncology Centre, General Hospital Sint-Augustinus</institution>, Wilrijk 2610,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">17117184</idno><idno type="pmc">2360768</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360768</idno><idno type="RBID">PMC:2360768</idno><idno type="doi">10.1038/sj.bjc.6603445</idno><date when="2006">2006</date><idno type="wicri:Area/Pmc/Corpus">000131</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000131</idno><idno type="wicri:Area/Pmc/Curation">000131</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000131</idno><idno type="wicri:Area/Pmc/Checkpoint">003C74</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">003C74</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours</title><author><name sortKey="Van Der Auwera, I" sort="Van Der Auwera, I" uniqKey="Van Der Auwera I" first="I" last="Van Der Auwera">I. Van Der Auwera</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Translational Cancer Research Group Antwerp, Laboratory of Pathology, University of Antwerp/University Hospital Antwerp, Edegem 2650, Belgium; Oncology Centre, General Hospital Sint-Augustinus</institution>, Wilrijk 2610,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cao, Y" sort="Cao, Y" uniqKey="Cao Y" first="Y" last="Cao">Y. Cao</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Laboratory of Angiogenesis Research, Microbiology and Tumor Biology Center, Karolinska Institutet</institution>, Stockholm 171 77,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Tille, J C" sort="Tille, J C" uniqKey="Tille J" first="J C" last="Tille">J C Tille</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Microbiology, Laboratory of Angiogenesis Research, Tumor and Cell Biology, Karolinska Institutet</institution>, Stockholm 171 77,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Pepper, M S" sort="Pepper, M S" uniqKey="Pepper M" first="M S" last="Pepper">M S Pepper</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>NetCare Molecular Medicine Institute, Unitas Hospital and Department of Immunology, Faculty of Health Sciences, University of Pretoria</institution>, Pretoria 0002,<country>South Africa</country></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jackson, D G" sort="Jackson, D G" uniqKey="Jackson D" first="D G" last="Jackson">D G Jackson</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital</institution>, Oxford OX3 9DS,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Fox, S B" sort="Fox, S B" uniqKey="Fox S" first="S B" last="Fox">S B Fox</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Department of Pathology, Peter MacCallum Cancer Centre</institution>, Victoria 8006,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Harris, A L" sort="Harris, A L" uniqKey="Harris A" first="A L" last="Harris">A L Harris</name><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Cancer Research UK Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital</institution>, Oxford OX3 9DS,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dirix, L Y" sort="Dirix, L Y" uniqKey="Dirix L" first="L Y" last="Dirix">L Y Dirix</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Translational Cancer Research Group Antwerp, Laboratory of Pathology, University of Antwerp/University Hospital Antwerp, Edegem 2650, Belgium; Oncology Centre, General Hospital Sint-Augustinus</institution>, Wilrijk 2610,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Vermeulen, P B" sort="Vermeulen, P B" uniqKey="Vermeulen P" first="P B" last="Vermeulen">P B Vermeulen</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Translational Cancer Research Group Antwerp, Laboratory of Pathology, University of Antwerp/University Hospital Antwerp, Edegem 2650, Belgium; Oncology Centre, General Hospital Sint-Augustinus</institution>, Wilrijk 2610,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">British Journal of Cancer</title><idno type="ISSN">0007-0920</idno><idno type="eISSN">1532-1827</idno><imprint><date when="2006">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The lymphatic system is the primary pathway of metastasis for most human cancers. Recent research efforts in studying lymphangiogenesis have suggested the existence of a relationship between lymphatic vessel density and patient survival. However, current methodology of lymphangiogenesis quantification is still characterised by high intra- and interobserver variability. For the amount of lymphatic vessels in a tumour to be a clinically useful parameter, a reliable quantification technique needs to be developed. With this consensus report, we therefore would like to initiate discussion on the standardisation of the immunohistochemical method for lymphangiogenesis assessment.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
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<front><journal-meta><journal-id journal-id-type="nlm-ta">Br J Cancer</journal-id><journal-title>British Journal of Cancer</journal-title><issn pub-type="ppub">0007-0920</issn><issn pub-type="epub">1532-1827</issn></journal-meta><article-meta><article-id pub-id-type="pmid">17117184</article-id><article-id pub-id-type="pmc">2360768</article-id><article-id pub-id-type="pii">6603445</article-id><article-id pub-id-type="doi">10.1038/sj.bjc.6603445</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Van der Auwera</surname><given-names>I</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Cao</surname><given-names>Y</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Tille</surname><given-names>J C</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Pepper</surname><given-names>M S</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Jackson</surname><given-names>D G</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Fox</surname><given-names>S B</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Harris</surname><given-names>A L</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Dirix</surname><given-names>L Y</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Vermeulen</surname><given-names>P B</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="corresp" rid="caf1">*</xref></contrib></contrib-group><aff id="aff1"><label>1</label><institution>Translational Cancer Research Group Antwerp, Laboratory of Pathology, University of Antwerp/University Hospital Antwerp, Edegem 2650, Belgium; Oncology Centre, General Hospital Sint-Augustinus</institution>, Wilrijk 2610,<country>Belgium</country></aff><aff id="aff2"><label>2</label><institution>Laboratory of Angiogenesis Research, Microbiology and Tumor Biology Center, Karolinska Institutet</institution>, Stockholm 171 77,<country>Sweden</country></aff><aff id="aff3"><label>3</label><institution>Department of Microbiology, Laboratory of Angiogenesis Research, Tumor and Cell Biology, Karolinska Institutet</institution>, Stockholm 171 77,<country>Sweden</country></aff><aff id="aff4"><label>4</label><institution>NetCare Molecular Medicine Institute, Unitas Hospital and Department of Immunology, Faculty of Health Sciences, University of Pretoria</institution>, Pretoria 0002,<country>South Africa</country></aff><aff id="aff5"><label>5</label><institution>Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital</institution>, Oxford OX3 9DS,<country>UK</country></aff><aff id="aff6"><label>6</label><institution>Department of Pathology, Peter MacCallum Cancer Centre</institution>, Victoria 8006,<country>Australia</country></aff><aff id="aff7"><label>7</label><institution>Cancer Research UK Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital</institution>, Oxford OX3 9DS,<country>UK</country></aff><author-notes><corresp id="caf1"><label>*</label>Author for correspondence: <email xlink:href="mailto:peter.vermeulen@gvagroup.be">peter.vermeulen@gvagroup.be</email></corresp></author-notes><pub-date pub-type="epub"><day>12</day><month>12</month><year>2006</year></pub-date><pub-date pub-type="ppub"><day>18</day><month>12</month><year>2006</year></pub-date><volume>95</volume><issue>12</issue><fpage>1611</fpage><lpage>1625</lpage><history><date date-type="received"><day>24</day><month>05</month><year>2006</year></date><date date-type="rev-recd"><day>18</day><month>09</month><year>2006</year></date><date date-type="accepted"><day>26</day><month>09</month><year>2006</year></date></history><copyright-statement>Copyright 2006, Cancer Research UK</copyright-statement><copyright-year>2006</copyright-year><permissions><copyright-holder>Cancer Research UK</copyright-holder></permissions><abstract><p>The lymphatic system is the primary pathway of metastasis for most human cancers. Recent research efforts in studying lymphangiogenesis have suggested the existence of a relationship between lymphatic vessel density and patient survival. However, current methodology of lymphangiogenesis quantification is still characterised by high intra- and interobserver variability. For the amount of lymphatic vessels in a tumour to be a clinically useful parameter, a reliable quantification technique needs to be developed. With this consensus report, we therefore would like to initiate discussion on the standardisation of the immunohistochemical method for lymphangiogenesis assessment.</p></abstract><kwd-group><kwd>lymphangiogenesis</kwd><kwd>lymphatic vessel density (LVD)</kwd><kwd>lymphatic endothelial cell proliferation (LECP)</kwd><kwd>podoplanin</kwd><kwd>lymph node metastasis</kwd><kwd>vascular endothelial growth factor (VEGF)</kwd></kwd-group></article-meta></front><floats-wrap><fig id="fig1"><label>Figure 1</label><caption><p>Lymphangiogenic growth factors and their receptors.</p></caption><graphic mime-subtype="jpeg" xlink:href="95-6603445f1"></graphic></fig><fig id="fig2"><label>Figure 2</label><caption><p>Representation of lymphangiogenic markers on lymphatic endothelial cells.</p></caption><graphic mime-subtype="jpeg" xlink:href="95-6603445f2"></graphic></fig><table-wrap id="tbl1" position="float"><label>Table 1</label><caption><p content-type="table-title">Molecular players of lymphangiogenesis</p></caption><table frame="hsides" rules="groups" border="1" width="85%"><colgroup><col align="left"></col><col align="left"></col><col align="left"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><bold>Gene</bold></th><th align="left" valign="top" charoff="50"><bold>Involvement in lymphangiogenesis</bold></th><th align="left" valign="top" charoff="50"><bold>Reference</bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50"><italic>VEGF-C</italic></td><td align="left" valign="top" charoff="50">Essential for sprouting the first lymphatic vessel from Prox-1-positive endothelial cells of veins</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib61">Karkkainen <italic>et al</italic> (2004)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Overexpression in mouse tumour models promotes the growth of intratumourous lymphatic vessels and metastasis to regional lymph nodes</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib123">Skobe <italic>et al</italic> (2001)</xref>, <xref ref-type="other" rid="bib62">Karpanen <italic>et al</italic> (2001)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"><italic>VEGF-D</italic></td><td align="left" valign="top" charoff="50">Overexpression in mouse tumour models induces the formation of lymphatic vessels within the tumour and leads to spread of the tumour to lymph nodes</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib126">Stacker <italic>et al</italic> (2001)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"><italic>VEGFR-3</italic></td><td align="left" valign="top" charoff="50">Plays an important role in the development of the lymphatic vasculature</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib60">Karkkainen <italic>et al</italic> (2000)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Induces proliferation of cultured LECs</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib79">Mäkinen <italic>et al</italic> (2001)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Induces lymphangiogenesis in transgenic mice</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib144">Veikkola <italic>et al</italic> (2001)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"><italic>VEGF-A</italic></td><td align="left" valign="top" charoff="50">Overexpression in mouse tumour models induces the growth of peritumourous lymphatic vessels and leads to lymphatic metastasis</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib12">Bjorndahl <italic>et al</italic> (2005b)</xref>, <xref ref-type="other" rid="bib46">Hirakawa <italic>et al</italic> (2005)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">VEGFR-2 is expressed in LECs</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib48">Hong <italic>et al</italic> (2004)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Can induce lymphangiogenesis indirectly by recruiting VEGFR-1 expressing inflammatory cells including monocytes/macrophages and neutrophils</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib26">Cursiefen <italic>et al</italic> (2004)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"><italic>FGF-2</italic></td><td align="left" valign="top" charoff="50">Stimulates proliferation, migration and tube formation of cultured LECs</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib21">Chang <italic>et al</italic> (2004)</xref>, <xref ref-type="other" rid="bib121">Shin <italic>et al</italic> (2005)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Induces sprouting of lymphatic vessels in a mouse corneal model can induce lymphangiogenesis indirectly by recruiting inflammatory cells</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib21">Chang <italic>et al</italic> (2004)</xref>, <xref ref-type="other" rid="bib68">Kubo <italic>et al</italic> (2002)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"><italic>PDGF-BB</italic></td><td align="left" valign="top" charoff="50">Stimulates cell motility of cultured LECs</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib17">Cao <italic>et al</italic> (2004)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Isolated LECs express both PDGFR-alpha and beta</td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Overexpression in a mouse tumour model stimulates the growth of intratumourous lymphatic vessels and lymphatic metastasis</td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"><italic>Ang-2</italic></td><td align="left" valign="top" charoff="50">Ang-2-knockout mice show disorganised and hypoplastic dermal and intestinal lymphatic capillaries</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib36">Gale <italic>et al</italic> (2002)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"><italic>Ang-1</italic></td><td align="left" valign="top" charoff="50">Restores lymphatic defects of Ang-2-knock-out mice</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib36">Gale <italic>et al</italic> (2002)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Promotes LYVE-1-positive lymphatic vessel formation in murine cornea</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib88">Morisada <italic>et al</italic> (2005)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"><italic>HGF</italic></td><td align="left" valign="top" charoff="50">Stimulates proliferation, migration and tube formation of cultured LECs</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib59">Kajiya <italic>et al</italic> (2005)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Induces sprouting and growth of new LYVE-1 expressing lymphatic vessels in mice corneal and tumour models</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib16">Cao <italic>et al</italic> (2006)</xref>, <xref ref-type="other" rid="bib53">Jiang <italic>et al</italic> (2005)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"><italic>IGF-1</italic></td><td align="left" valign="top" charoff="50">Stimulates proliferation and migration of cultured LECs</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib11">Bjorndahl <italic>et al</italic> (2005a)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">IGFR-1 is present in lymphatic endothelium</td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Induces growth of new LYVE-1 expressing lymphatic vessels in murine cornea</td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"><italic>IGF-2</italic></td><td align="left" valign="top" charoff="50">Stimulates proliferation and migration of cultured LECs</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib11">Bjorndahl <italic>et al</italic> (2005a)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">IGFR-1 and -2 are present in lymphatic endothelium</td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Induces growth of new LYVE-1 expressing lymphatic vessels in murine cornea</td><td align="left" valign="top" charoff="50"> </td></tr></tbody></table></table-wrap><table-wrap id="tbl2" position="float"><label>Table 2</label><caption><p content-type="table-title">List of studies on the prognostic value of lymphangiogenesis in solid human tumours</p></caption><graphic xlink:href="95-6603445t1"></graphic></table-wrap><table-wrap id="tbl3" position="float"><label>Table 3</label><caption><p content-type="table-title">Studies on circulating VEGF-C and VEGF-D levels in patients with cancer</p></caption><table frame="hsides" rules="groups" border="1" width="85%"><colgroup><col align="left"></col><col align="left"></col><col align="left"></col><col align="left"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><bold>Tumour</bold></th><th align="left" valign="top" charoff="50"><bold>Markers (source)</bold></th><th align="left" valign="top" charoff="50"><bold>Comments</bold></th><th align="left" valign="top" charoff="50"><bold>Reference</bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50"><italic>Colorectal ca.</italic></td><td align="left" valign="top" charoff="50">VEGF-C (plasma)</td><td align="left" valign="top" charoff="50">Increased in cancer patient compared to control</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib30">Duff <italic>et al</italic> (2003)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Significantly higher in advanced Dukes C and D (LN+) compared to Dukes A and B (LN−)</td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">VEGF-C (plasma)</td><td align="left" valign="top" charoff="50">Decreased expression in cancer patient compare to control</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib31">Duff <italic>et al</italic> (2005)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">VEGF-D (serum)</td><td align="left" valign="top" charoff="50">No difference between cancer and control</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib38">George <italic>et al</italic> (2001)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">VEGF-D (plasma)</td><td align="left" valign="top" charoff="50">No difference between cancer and control</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib31">Duff <italic>et al</italic> (2005)</xref></td></tr><tr><td align="left" valign="top" charoff="50"><italic>Non-small cell lung ca.</italic></td><td align="left" valign="top" charoff="50">VEGF-C (serum)</td><td align="left" valign="top" charoff="50">Increased in carcinoma compared to benign lesions and control individuals</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib134">Tamura and Ohta (2003)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Correlation with pathologic stage, LN metastasis and lymphatic vessel invasion</td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">VEGF-C (serum)</td><td align="left" valign="top" charoff="50">Correlation with pathologic stage, LN metastasis and lymphatic vessel invasion</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib132">Tamura <italic>et al</italic> (2004a</xref>, <xref ref-type="other" rid="bib132">2004b</xref>)</td></tr><tr><td align="left" valign="top" charoff="50"><italic>Cervical ca.</italic></td><td align="left" valign="top" charoff="50">VEGF-C (serum)</td><td align="left" valign="top" charoff="50">Increased in squamous cervical cancer compared to controls</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib86">Mitsuhashi <italic>et al</italic> (2005)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Correlation with FIGO stage, tumour size and recurrence but not with LN metastasis</td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">No increase in cervical adenocarcinoma compared to controls</td><td align="left" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">VEGF-C (serum)</td><td align="left" valign="top" charoff="50">Increased in cervical cancer compared to controls</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib83">Mathur <italic>et al</italic> (2005)</xref></td></tr><tr><td align="left" valign="top" charoff="50"><italic>Prostate ca.</italic></td><td align="left" valign="top" charoff="50">VEGF-D (plasma)</td><td align="left" valign="top" charoff="50">Increased in early stage (LN neg) compare to late stage (LN or bone) metastasis</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib64">Kaushal <italic>et al</italic> (2005)</xref></td></tr><tr><td align="left" valign="top" charoff="50"><italic>Angiosarcoma</italic></td><td align="left" valign="top" charoff="50">VEGF-D (serum)</td><td align="left" valign="top" charoff="50">Increased compared to controls</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib5">Amo <italic>et al</italic> (2004)</xref></td></tr><tr><td align="left" valign="top" charoff="50"><italic>Ovarian ca.</italic></td><td align="left" valign="top" charoff="50">VEGF-C (serum)</td><td align="left" valign="top" charoff="50">Not increased compared to controls</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib83">Mathur <italic>et al</italic> (2005)</xref></td></tr><tr><td align="left" valign="top" charoff="50"><italic>Breast ca.</italic></td><td align="left" valign="top" charoff="50">VEGF-D (plasma)</td><td align="left" valign="top" charoff="50">Not increased compared to controls</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib47">Hoar <italic>et al</italic> (2004)</xref></td></tr><tr><td align="left" valign="top" charoff="50"><italic>Head and neck ca.</italic></td><td align="left" valign="top" charoff="50">VEGF-C (plasma)</td><td align="left" valign="top" charoff="50">Not increased compared to controls</td><td align="left" valign="top" charoff="50"><xref ref-type="other" rid="bib129">Strauss <italic>et al</italic> (2005)</xref></td></tr></tbody></table></table-wrap><table-wrap id="tbl4" position="float"><label>Table 4</label><caption><p content-type="table-title">Proposed standard method for the assessment of lymphangiogenesis</p></caption><table frame="hsides" rules="groups" border="1" width="85%"><colgroup><col align="left"></col><col align="left"></col><col align="left"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><bold>Methodological aspect</bold></th><th align="left" valign="top" charoff="50"><bold>Proposed standard</bold></th><th align="left" valign="top" charoff="50"><bold>Advantage</bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50">1. Immunostaining</td><td align="left" valign="top" charoff="50">Double immunostain with the D2-40 monoclonal antibody and the anti-Ki-67 monoclonal antibody</td><td align="left" valign="top" charoff="50">Highly specific and sensitive marker of the lymphatic endothelium</td></tr><tr><td align="left" valign="top" charoff="50">2. Selection of the quantification fields</td><td align="left" valign="top" charoff="50">Manual vascular hot spot selection at low magnification (e.g. × 10) – in viable tumour tissue and adjacent (e.g. within diameter of one field at × 200 magnification) stromal tissue</td><td align="left" valign="top" charoff="50">All highly vascular areas can be detected</td></tr><tr><td align="left" valign="top" charoff="50">3. Quantification of lymphatic vessels</td><td align="left" valign="top" charoff="50">Chalkley point graticule method</td><td align="left" valign="top" charoff="50">Exclusion of the subjective step of identifying individual lymphatic vessels in an endothelial cell cluster</td></tr><tr><td align="left" valign="top" charoff="50">4. Quantification of LEC proliferation</td><td align="left" valign="top" charoff="50">Counting of the number of proliferating LECs <italic>vs</italic> nonproliferating LECs</td><td align="left" valign="top" charoff="50">Reflection of the ongoing lymphangiogenesis</td></tr><tr><td align="left" valign="top" charoff="50">5. Number of observers</td><td align="left" valign="top" charoff="50">Sequential assessment by two investigators</td><td align="left" valign="top" charoff="50">More practical in a clinical setting than co-observation</td></tr></tbody></table></table-wrap></floats-wrap></pmc><affiliations><list><country><li>Afrique du Sud</li><li>Australie</li><li>Belgique</li><li>Royaume-Uni</li><li>Suède</li></country></list><tree><country name="Belgique"><noRegion><name sortKey="Van Der Auwera, I" sort="Van Der Auwera, I" uniqKey="Van Der Auwera I" first="I" last="Van Der Auwera">I. Van Der Auwera</name></noRegion><name sortKey="Dirix, L Y" sort="Dirix, L Y" uniqKey="Dirix L" first="L Y" last="Dirix">L Y Dirix</name><name sortKey="Vermeulen, P B" sort="Vermeulen, P B" uniqKey="Vermeulen P" first="P B" last="Vermeulen">P B Vermeulen</name></country><country name="Suède"><noRegion><name sortKey="Cao, Y" sort="Cao, Y" uniqKey="Cao Y" first="Y" last="Cao">Y. Cao</name></noRegion><name sortKey="Tille, J C" sort="Tille, J C" uniqKey="Tille J" first="J C" last="Tille">J C Tille</name></country><country name="Afrique du Sud"><noRegion><name sortKey="Pepper, M S" sort="Pepper, M S" uniqKey="Pepper M" first="M S" last="Pepper">M S Pepper</name></noRegion></country><country name="Royaume-Uni"><noRegion><name sortKey="Jackson, D G" sort="Jackson, D G" uniqKey="Jackson D" first="D G" last="Jackson">D G Jackson</name></noRegion><name sortKey="Harris, A L" sort="Harris, A L" uniqKey="Harris A" first="A L" last="Harris">A L Harris</name></country><country name="Australie"><noRegion><name sortKey="Fox, S B" sort="Fox, S B" uniqKey="Fox S" first="S B" last="Fox">S B Fox</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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