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<title xml:lang="en">Pregnancy Promotes Melanoma Metastasis through Enhanced Lymphangiogenesis</title>
<author>
<name sortKey="Khosrotehrani, Kiarash" sort="Khosrotehrani, Kiarash" uniqKey="Khosrotehrani K" first="Kiarash" last="Khosrotehrani">Kiarash Khosrotehrani</name>
<affiliation>
<nlm:aff id="aff1">Université Pierre et Marie Curie, University Paris 06, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">INSERM UMR_S938, Centre de Recherche Saint Antoine, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff3">Department of Dermatology, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff6">Experimental Dermatology Group, University of Queensland Centre for Clinical Research, Brisbane, Australia</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Huu, Sau Nguyen" sort="Huu, Sau Nguyen" uniqKey="Huu S" first="Sau Nguyen" last="Huu">Sau Nguyen Huu</name>
<affiliation>
<nlm:aff id="aff1">Université Pierre et Marie Curie, University Paris 06, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">INSERM UMR_S938, Centre de Recherche Saint Antoine, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Prignon, Aurelie" sort="Prignon, Aurelie" uniqKey="Prignon A" first="Aurélie" last="Prignon">Aurélie Prignon</name>
<affiliation>
<nlm:aff id="aff1">Université Pierre et Marie Curie, University Paris 06, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">INSERM UMR_S938, Centre de Recherche Saint Antoine, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Avril, Marie Francoise" sort="Avril, Marie Francoise" uniqKey="Avril M" first="Marie-Françoise" last="Avril">Marie-Françoise Avril</name>
<affiliation>
<nlm:aff id="aff7">Department of Dermatology, Assistance Publique Hôpitaux de Paris, Hôpital Tarnier, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Boitier, Francoise" sort="Boitier, Francoise" uniqKey="Boitier F" first="Françoise" last="Boitier">Françoise Boitier</name>
<affiliation>
<nlm:aff id="aff7">Department of Dermatology, Assistance Publique Hôpitaux de Paris, Hôpital Tarnier, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Oster, Michele" sort="Oster, Michele" uniqKey="Oster M" first="Michèle" last="Oster">Michèle Oster</name>
<affiliation>
<nlm:aff id="aff1">Université Pierre et Marie Curie, University Paris 06, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">INSERM UMR_S938, Centre de Recherche Saint Antoine, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Mortier, Laurent" sort="Mortier, Laurent" uniqKey="Mortier L" first="Laurent" last="Mortier">Laurent Mortier</name>
<affiliation>
<nlm:aff id="aff8">Department of Dermatology, CHRU Lille, Hôpital Claude Huriez, Lille, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Richard, Marie Aleth" sort="Richard, Marie Aleth" uniqKey="Richard M" first="Marie-Aleth" last="Richard">Marie-Aleth Richard</name>
<affiliation>
<nlm:aff id="aff9">Department of Dermatology, Assistance Publique-Hôpitaux de Marseille, CHU Sainte-Marguerite, Marseille, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Maubec, Eve" sort="Maubec, Eve" uniqKey="Maubec E" first="Eve" last="Maubec">Eve Maubec</name>
<affiliation>
<nlm:aff id="aff10">Department of Dermatology, Assistance Publique Hôpitaux de Paris, Hôpital Bichat, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Kerob, Delphine" sort="Kerob, Delphine" uniqKey="Kerob D" first="Delphine" last="Kerob">Delphine Kerob</name>
<affiliation>
<nlm:aff id="aff11">Department of Dermatology, Assistance Publique Hôpitaux de Paris, Hôpital Saint-Louis, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Mansard, Sandrine" sort="Mansard, Sandrine" uniqKey="Mansard S" first="Sandrine" last="Mansard">Sandrine Mansard</name>
<affiliation>
<nlm:aff id="aff12">Department of Dermatology, Université d'Auvergne Clermont-Ferrand 1, CHU Hôtel-Dieu, Clermont-Ferrand, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Merheb, Charbel" sort="Merheb, Charbel" uniqKey="Merheb C" first="Charbel" last="Merheb">Charbel Merheb</name>
<affiliation>
<nlm:aff id="aff4">Department of Nuclear Medicine, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Moguelet, Philippe" sort="Moguelet, Philippe" uniqKey="Moguelet P" first="Philippe" last="Moguelet">Philippe Moguelet</name>
<affiliation>
<nlm:aff id="aff5">Department of Pathology, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Nassar, Dany" sort="Nassar, Dany" uniqKey="Nassar D" first="Dany" last="Nassar">Dany Nassar</name>
<affiliation>
<nlm:aff id="aff1">Université Pierre et Marie Curie, University Paris 06, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Guegan, Sarah" sort="Guegan, Sarah" uniqKey="Guegan S" first="Sarah" last="Guégan">Sarah Guégan</name>
<affiliation>
<nlm:aff id="aff1">Université Pierre et Marie Curie, University Paris 06, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">INSERM UMR_S938, Centre de Recherche Saint Antoine, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff3">Department of Dermatology, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Aractingi, Selim" sort="Aractingi, Selim" uniqKey="Aractingi S" first="Selim" last="Aractingi">Selim Aractingi</name>
<affiliation>
<nlm:aff id="aff1">Université Pierre et Marie Curie, University Paris 06, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">INSERM UMR_S938, Centre de Recherche Saint Antoine, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff3">Department of Dermatology, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France</nlm:aff>
</affiliation>
</author>
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<idno type="pmid">21435464</idno>
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<idno type="doi">10.1016/j.ajpath.2010.12.044</idno>
<date when="2011">2011</date>
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<title xml:lang="en" level="a" type="main">Pregnancy Promotes Melanoma Metastasis through Enhanced Lymphangiogenesis</title>
<author>
<name sortKey="Khosrotehrani, Kiarash" sort="Khosrotehrani, Kiarash" uniqKey="Khosrotehrani K" first="Kiarash" last="Khosrotehrani">Kiarash Khosrotehrani</name>
<affiliation>
<nlm:aff id="aff1">Université Pierre et Marie Curie, University Paris 06, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">INSERM UMR_S938, Centre de Recherche Saint Antoine, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff3">Department of Dermatology, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff6">Experimental Dermatology Group, University of Queensland Centre for Clinical Research, Brisbane, Australia</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Huu, Sau Nguyen" sort="Huu, Sau Nguyen" uniqKey="Huu S" first="Sau Nguyen" last="Huu">Sau Nguyen Huu</name>
<affiliation>
<nlm:aff id="aff1">Université Pierre et Marie Curie, University Paris 06, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">INSERM UMR_S938, Centre de Recherche Saint Antoine, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Prignon, Aurelie" sort="Prignon, Aurelie" uniqKey="Prignon A" first="Aurélie" last="Prignon">Aurélie Prignon</name>
<affiliation>
<nlm:aff id="aff1">Université Pierre et Marie Curie, University Paris 06, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">INSERM UMR_S938, Centre de Recherche Saint Antoine, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Avril, Marie Francoise" sort="Avril, Marie Francoise" uniqKey="Avril M" first="Marie-Françoise" last="Avril">Marie-Françoise Avril</name>
<affiliation>
<nlm:aff id="aff7">Department of Dermatology, Assistance Publique Hôpitaux de Paris, Hôpital Tarnier, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Boitier, Francoise" sort="Boitier, Francoise" uniqKey="Boitier F" first="Françoise" last="Boitier">Françoise Boitier</name>
<affiliation>
<nlm:aff id="aff7">Department of Dermatology, Assistance Publique Hôpitaux de Paris, Hôpital Tarnier, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Oster, Michele" sort="Oster, Michele" uniqKey="Oster M" first="Michèle" last="Oster">Michèle Oster</name>
<affiliation>
<nlm:aff id="aff1">Université Pierre et Marie Curie, University Paris 06, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">INSERM UMR_S938, Centre de Recherche Saint Antoine, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Mortier, Laurent" sort="Mortier, Laurent" uniqKey="Mortier L" first="Laurent" last="Mortier">Laurent Mortier</name>
<affiliation>
<nlm:aff id="aff8">Department of Dermatology, CHRU Lille, Hôpital Claude Huriez, Lille, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Richard, Marie Aleth" sort="Richard, Marie Aleth" uniqKey="Richard M" first="Marie-Aleth" last="Richard">Marie-Aleth Richard</name>
<affiliation>
<nlm:aff id="aff9">Department of Dermatology, Assistance Publique-Hôpitaux de Marseille, CHU Sainte-Marguerite, Marseille, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Maubec, Eve" sort="Maubec, Eve" uniqKey="Maubec E" first="Eve" last="Maubec">Eve Maubec</name>
<affiliation>
<nlm:aff id="aff10">Department of Dermatology, Assistance Publique Hôpitaux de Paris, Hôpital Bichat, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Kerob, Delphine" sort="Kerob, Delphine" uniqKey="Kerob D" first="Delphine" last="Kerob">Delphine Kerob</name>
<affiliation>
<nlm:aff id="aff11">Department of Dermatology, Assistance Publique Hôpitaux de Paris, Hôpital Saint-Louis, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Mansard, Sandrine" sort="Mansard, Sandrine" uniqKey="Mansard S" first="Sandrine" last="Mansard">Sandrine Mansard</name>
<affiliation>
<nlm:aff id="aff12">Department of Dermatology, Université d'Auvergne Clermont-Ferrand 1, CHU Hôtel-Dieu, Clermont-Ferrand, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Merheb, Charbel" sort="Merheb, Charbel" uniqKey="Merheb C" first="Charbel" last="Merheb">Charbel Merheb</name>
<affiliation>
<nlm:aff id="aff4">Department of Nuclear Medicine, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Moguelet, Philippe" sort="Moguelet, Philippe" uniqKey="Moguelet P" first="Philippe" last="Moguelet">Philippe Moguelet</name>
<affiliation>
<nlm:aff id="aff5">Department of Pathology, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Nassar, Dany" sort="Nassar, Dany" uniqKey="Nassar D" first="Dany" last="Nassar">Dany Nassar</name>
<affiliation>
<nlm:aff id="aff1">Université Pierre et Marie Curie, University Paris 06, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Guegan, Sarah" sort="Guegan, Sarah" uniqKey="Guegan S" first="Sarah" last="Guégan">Sarah Guégan</name>
<affiliation>
<nlm:aff id="aff1">Université Pierre et Marie Curie, University Paris 06, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">INSERM UMR_S938, Centre de Recherche Saint Antoine, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff3">Department of Dermatology, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Aractingi, Selim" sort="Aractingi, Selim" uniqKey="Aractingi S" first="Selim" last="Aractingi">Selim Aractingi</name>
<affiliation>
<nlm:aff id="aff1">Université Pierre et Marie Curie, University Paris 06, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">INSERM UMR_S938, Centre de Recherche Saint Antoine, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff3">Department of Dermatology, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France</nlm:aff>
</affiliation>
</author>
</analytic>
<series>
<title level="j">The American Journal of Pathology</title>
<idno type="ISSN">0002-9440</idno>
<idno type="eISSN">1525-2191</idno>
<imprint>
<date when="2011">2011</date>
</imprint>
</series>
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<front>
<div type="abstract" xml:lang="en">
<p>The relationships of pregnancy and melanoma have been debatable. Our aim was to assess the influence of gestation on the course of melanoma in a classic murine model of tumor progression and in women. B16 mouse melanoma cells were injected in nonpregnant or pregnant mice on day 5 of gestation. Animals were evaluated for tumor progression, metastases, and survival. Tumor sections were analyzed for lymphatic and blood vessel number and relative surface and expression of angiogenic growth factors. Finally, primary melanomas from pregnant and nonpregnant women, matched for age and tumor thickness, were also considered. Tumor growth, metastasis, and mortality were increased in B16-injected pregnant mice. Tumors displayed an increase in intratumoral lymphangiogenesis during gestation. This increased lymphatic angiogenesis was not observed in normal skin during gestation, showing its specificity to the tumor. An analysis of melanoma from pregnant and matched nonpregnant women showed a similar increase in lymphatic vessels. Tumors from pregnant mice had increased expression of vascular endothelial growth factor A at the RNA and protein levels. The increased vascular endothelial growth factor A production by melanoma cells could be reproduced in culture using pregnant mouse serum. In conclusion, pregnancy results in increased lymphangiogenesis and subsequent metastasis. Caution should be applied in the management of patients with advanced-stage melanoma during gestation.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Am J Pathol</journal-id>
<journal-title-group>
<journal-title>The American Journal of Pathology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0002-9440</issn>
<issn pub-type="epub">1525-2191</issn>
<publisher>
<publisher-name>American Society for Investigative Pathology</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">21435464</article-id>
<article-id pub-id-type="pmc">3078435</article-id>
<article-id pub-id-type="publisher-id">AJPA219</article-id>
<article-id pub-id-type="doi">10.1016/j.ajpath.2010.12.044</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Regular Article</subject>
<subj-group>
<subject>Tumorigenesis and Neoplastic Progression</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Pregnancy Promotes Melanoma Metastasis through Enhanced Lymphangiogenesis</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Khosrotehrani</surname>
<given-names>Kiarash</given-names>
</name>
<xref rid="aff1" ref-type="aff"></xref>
<xref rid="aff2" ref-type="aff"></xref>
<xref rid="aff3" ref-type="aff"></xref>
<xref rid="aff6" ref-type="aff">§</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Huu</surname>
<given-names>Sau Nguyen</given-names>
</name>
<xref rid="aff1" ref-type="aff"></xref>
<xref rid="aff2" ref-type="aff"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Prignon</surname>
<given-names>Aurélie</given-names>
</name>
<xref rid="aff1" ref-type="aff"></xref>
<xref rid="aff2" ref-type="aff"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Avril</surname>
<given-names>Marie-Françoise</given-names>
</name>
<xref rid="aff7" ref-type="aff"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Boitier</surname>
<given-names>Françoise</given-names>
</name>
<xref rid="aff7" ref-type="aff"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Oster</surname>
<given-names>Michèle</given-names>
</name>
<xref rid="aff1" ref-type="aff"></xref>
<xref rid="aff2" ref-type="aff"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mortier</surname>
<given-names>Laurent</given-names>
</name>
<xref rid="aff8" ref-type="aff"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Richard</surname>
<given-names>Marie-Aleth</given-names>
</name>
<xref rid="aff9" ref-type="aff">⁎⁎</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Maubec</surname>
<given-names>Eve</given-names>
</name>
<xref rid="aff10" ref-type="aff">††</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kerob</surname>
<given-names>Delphine</given-names>
</name>
<xref rid="aff11" ref-type="aff">‡‡</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mansard</surname>
<given-names>Sandrine</given-names>
</name>
<xref rid="aff12" ref-type="aff">§§</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Merheb</surname>
<given-names>Charbel</given-names>
</name>
<xref rid="aff4" ref-type="aff">¶¶</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Moguelet</surname>
<given-names>Philippe</given-names>
</name>
<xref rid="aff5" ref-type="aff">∥∥</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Nassar</surname>
<given-names>Dany</given-names>
</name>
<xref rid="aff1" ref-type="aff"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Guégan</surname>
<given-names>Sarah</given-names>
</name>
<xref rid="aff1" ref-type="aff"></xref>
<xref rid="aff2" ref-type="aff"></xref>
<xref rid="aff3" ref-type="aff"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Aractingi</surname>
<given-names>Selim</given-names>
</name>
<email>selim.aractingi@gmail.com</email>
<xref rid="aff1" ref-type="aff"></xref>
<xref rid="aff2" ref-type="aff"></xref>
<xref rid="aff3" ref-type="aff"></xref>
<xref rid="cor1" ref-type="corresp"></xref>
</contrib>
</contrib-group>
<aff id="aff1">
<label></label>
Université Pierre et Marie Curie, University Paris 06, Paris, France</aff>
<aff id="aff2">
<label></label>
INSERM UMR_S938, Centre de Recherche Saint Antoine, Paris, France</aff>
<aff id="aff3">
<label></label>
Department of Dermatology, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France</aff>
<aff id="aff4">
<label>¶¶</label>
Department of Nuclear Medicine, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France</aff>
<aff id="aff5">
<label>∥∥</label>
Department of Pathology, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France</aff>
<aff id="aff6">
<label>§</label>
Experimental Dermatology Group, University of Queensland Centre for Clinical Research, Brisbane, Australia</aff>
<aff id="aff7">
<label></label>
Department of Dermatology, Assistance Publique Hôpitaux de Paris, Hôpital Tarnier, Paris, France</aff>
<aff id="aff8">
<label></label>
Department of Dermatology, CHRU Lille, Hôpital Claude Huriez, Lille, France</aff>
<aff id="aff9">
<label>⁎⁎</label>
Department of Dermatology, Assistance Publique-Hôpitaux de Marseille, CHU Sainte-Marguerite, Marseille, France</aff>
<aff id="aff10">
<label>††</label>
Department of Dermatology, Assistance Publique Hôpitaux de Paris, Hôpital Bichat, Paris, France</aff>
<aff id="aff11">
<label>‡‡</label>
Department of Dermatology, Assistance Publique Hôpitaux de Paris, Hôpital Saint-Louis, Paris, France</aff>
<aff id="aff12">
<label>§§</label>
Department of Dermatology, Université d'Auvergne Clermont-Ferrand 1, CHU Hôtel-Dieu, Clermont-Ferrand, France</aff>
<author-notes>
<corresp id="cor1">
<label></label>
Address reprint requests to Selim Aractingi, M.D., Ph.D., Université Paris 6, 27 rue de Chaligny, 75012 Paris, France
<email>selim.aractingi@gmail.com</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub">
<month>4</month>
<year>2011</year>
</pub-date>
<volume>178</volume>
<issue>4</issue>
<fpage>1870</fpage>
<lpage>1880</lpage>
<history>
<date date-type="accepted">
<day>30</day>
<month>12</month>
<year>2010</year>
</date>
</history>
<permissions>
<copyright-statement>© 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.</copyright-statement>
<copyright-year>2011</copyright-year>
<copyright-holder>American Society for Investigative Pathology</copyright-holder>
</permissions>
<abstract>
<p>The relationships of pregnancy and melanoma have been debatable. Our aim was to assess the influence of gestation on the course of melanoma in a classic murine model of tumor progression and in women. B16 mouse melanoma cells were injected in nonpregnant or pregnant mice on day 5 of gestation. Animals were evaluated for tumor progression, metastases, and survival. Tumor sections were analyzed for lymphatic and blood vessel number and relative surface and expression of angiogenic growth factors. Finally, primary melanomas from pregnant and nonpregnant women, matched for age and tumor thickness, were also considered. Tumor growth, metastasis, and mortality were increased in B16-injected pregnant mice. Tumors displayed an increase in intratumoral lymphangiogenesis during gestation. This increased lymphatic angiogenesis was not observed in normal skin during gestation, showing its specificity to the tumor. An analysis of melanoma from pregnant and matched nonpregnant women showed a similar increase in lymphatic vessels. Tumors from pregnant mice had increased expression of vascular endothelial growth factor A at the RNA and protein levels. The increased vascular endothelial growth factor A production by melanoma cells could be reproduced in culture using pregnant mouse serum. In conclusion, pregnancy results in increased lymphangiogenesis and subsequent metastasis. Caution should be applied in the management of patients with advanced-stage melanoma during gestation.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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