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<div class="action-panel-control-wrap">
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To:
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<div class="action-panel-control-wrap">
<label for="email-from" class="action-panel-label">
From:
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<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
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<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
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<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
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<button class="action-panel-submit"
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data-ga-category="save_share"
data-ga-action="email"
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Send email
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<button class="action-panel-cancel"
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ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
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</div>
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<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
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data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
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data-add-to-collection-max-amount="1000"
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<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
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value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
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<input
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id="collections-action-panel-add-to-new"
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maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
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<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
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<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
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<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
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<form id="saved-search-action-panel-form"
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data-create-saved-search-url="/create-saved-search/"
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Name of saved search:
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type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
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<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
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<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
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<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
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Frequency:
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<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
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<option value="Thursday">The first Thursday</option>
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Which day?
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<option value="Saturday">Saturday</option>
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<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
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<option value="MEDLINE">PubMed</option>
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<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
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<div>
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Send even when there aren't any new results
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<div class="action-panel-control-wrap option-text-in-email-wrap">
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Optional text in email:
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id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
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<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
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</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
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<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
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<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
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name="rss-name"
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class="rss-name"
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</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
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<option value="10">10</option>
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<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
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disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="25979631">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="http://jmg.bmj.com/lookup/pmidlookup?view=long&amp;pmid=25979631"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3051&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=25979631&amp;db=pubmed&amp;nlmid=2985087R"
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"
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target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=25979631&amp;db=pubmed&amp;nlmid=2985087R"
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Full text links
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</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
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data-citation-style="nlm"
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aria-label="Save article in MyNCBI collections."
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data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F25979631%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
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id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
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class="collections-existing"
name="collections"
value="existing"
checked="true"
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<h1 class="heading-title">
Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers
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34
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35
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37
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39
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1
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Affiliations
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<ul class="item-list">
<li data-affiliation-id="full-view-affiliation-1"
id="full-view-affiliation-1"
><sup class="key">1</sup> Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-2"
id="full-view-affiliation-2"
><sup class="key">2</sup> Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-3"
id="full-view-affiliation-3"
><sup class="key">3</sup> Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal Department of Pathology and Oncology, Medical Faculty of the University of Porto, Porto, Portugal Centro Hospitalar São João, Porto, Portugal.</li>
<li data-affiliation-id="full-view-affiliation-4"
id="full-view-affiliation-4"
><sup class="key">4</sup> Department of Biochemistry, University of Otago, Dunedin, New Zealand.</li>
<li data-affiliation-id="full-view-affiliation-5"
id="full-view-affiliation-5"
><sup class="key">5</sup> British Columbia Cancer Agency, Vancouver, British Columbia, Canada.</li>
<li data-affiliation-id="full-view-affiliation-6"
id="full-view-affiliation-6"
><sup class="key">6</sup> Department of Oncology, University of Cambridge, Cambridge, UK.</li>
<li data-affiliation-id="full-view-affiliation-7"
id="full-view-affiliation-7"
><sup class="key">7</sup> No Stomach For Cancer, Inc., Madison, Wisconsin, USA.</li>
<li data-affiliation-id="full-view-affiliation-8"
id="full-view-affiliation-8"
><sup class="key">8</sup> Department of Oesophago-Gastric Surgery, Addenbrooke&#x27;s Hospital, Cambridge, UK.</li>
<li data-affiliation-id="full-view-affiliation-9"
id="full-view-affiliation-9"
><sup class="key">9</sup> Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-10"
id="full-view-affiliation-10"
><sup class="key">10</sup> Department of Surgical Gastroenterology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.</li>
<li data-affiliation-id="full-view-affiliation-11"
id="full-view-affiliation-11"
><sup class="key">11</sup> Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.</li>
<li data-affiliation-id="full-view-affiliation-12"
id="full-view-affiliation-12"
><sup class="key">12</sup> Department of Gastroenterology, Radboud University Medical Center, Nijmegen, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-13"
id="full-view-affiliation-13"
><sup class="key">13</sup> Vinery Lane Surgery, Whangarei, New Zealand.</li>
<li data-affiliation-id="full-view-affiliation-14"
id="full-view-affiliation-14"
><sup class="key">14</sup> Division of Psychosocial Research and Epidemiology/Family Cancer Clinic, The Netherlands Cancer Institute, Amsterdam, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-15"
id="full-view-affiliation-15"
><sup class="key">15</sup> Sir Peter MacCallum Department of Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.</li>
<li data-affiliation-id="full-view-affiliation-16"
id="full-view-affiliation-16"
><sup class="key">16</sup> Department of Gastroenterology and Hepatology, Netherlands Cancer Institute/ Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-17"
id="full-view-affiliation-17"
><sup class="key">17</sup> Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.</li>
<li data-affiliation-id="full-view-affiliation-18"
id="full-view-affiliation-18"
><sup class="key">18</sup> The DeGregorio Family Foundation for Stomach and Esophageal Cancer Research, Pleasantville, New York, USA.</li>
<li data-affiliation-id="full-view-affiliation-19"
id="full-view-affiliation-19"
><sup class="key">19</sup> Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.</li>
<li data-affiliation-id="full-view-affiliation-20"
id="full-view-affiliation-20"
><sup class="key">20</sup> Division of Oncology, Stanford University School of Medicine, Stanford, California, USA.</li>
<li data-affiliation-id="full-view-affiliation-21"
id="full-view-affiliation-21"
><sup class="key">21</sup> Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-22"
id="full-view-affiliation-22"
><sup class="key">22</sup> Scientific Institute for Quality of Healthcare, Radboud University Medical Center, Nijmegen, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-23"
id="full-view-affiliation-23"
><sup class="key">23</sup> Division of Surgical Research, University of Zurich, Zurich, Suisse.</li>
<li data-affiliation-id="full-view-affiliation-24"
id="full-view-affiliation-24"
><sup class="key">24</sup> Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.</li>
<li data-affiliation-id="full-view-affiliation-25"
id="full-view-affiliation-25"
><sup class="key">25</sup> Institute of Pathology, Technische Universität, Munich, Germany.</li>
<li data-affiliation-id="full-view-affiliation-26"
id="full-view-affiliation-26"
><sup class="key">26</sup> Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-27"
id="full-view-affiliation-27"
><sup class="key">27</sup> Department of Histopathology, Cambridge University Hospitals NHS Trust, Cambridge, UK.</li>
<li data-affiliation-id="full-view-affiliation-28"
id="full-view-affiliation-28"
><sup class="key">28</sup> Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal Department of Pathology and Oncology, Medical Faculty of the University of Porto, Porto, Portugal.</li>
<li data-affiliation-id="full-view-affiliation-29"
id="full-view-affiliation-29"
><sup class="key">29</sup> NIHR Biomedical Research Unit, Nottingham Digestive Diseases Centre, Queens Medical Centre campus, Nottingham University Hospitals NHS Trust, Nottingham, UK.</li>
<li data-affiliation-id="full-view-affiliation-30"
id="full-view-affiliation-30"
><sup class="key">30</sup> Patient representative, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-31"
id="full-view-affiliation-31"
><sup class="key">31</sup> Department of Oncology, Familial Gastric Cancer Registry, Cambridge University Hospital, Cambridge, UK.</li>
<li data-affiliation-id="full-view-affiliation-32"
id="full-view-affiliation-32"
><sup class="key">32</sup> Department of General Surgery and Surgical Oncology, University of Siena, Siena, Italy.</li>
<li data-affiliation-id="full-view-affiliation-33"
id="full-view-affiliation-33"
><sup class="key">33</sup> Department of Surgical Research, Technical University Dresden, Dresden, Germany.</li>
<li data-affiliation-id="full-view-affiliation-34"
id="full-view-affiliation-34"
><sup class="key">34</sup> Cambridge University Hospital, Cambridge, UK.</li>
<li data-affiliation-id="full-view-affiliation-35"
id="full-view-affiliation-35"
><sup class="key">35</sup> Stichting CDH1, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-36"
id="full-view-affiliation-36"
><sup class="key">36</sup> Department of Medical Genetics, University of Cambridge, Cambridge, UK.</li>
<li data-affiliation-id="full-view-affiliation-37"
id="full-view-affiliation-37"
><sup class="key">37</sup> Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-38"
id="full-view-affiliation-38"
><sup class="key">38</sup> Department of Surgical Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-39"
id="full-view-affiliation-39"
><sup class="key">39</sup> Department of Surgery, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-40"
id="full-view-affiliation-40"
><sup class="key">40</sup> Radboud University Medical Center, Nijmegen, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-41"
id="full-view-affiliation-41"
><sup class="key">41</sup> Cambridge NIHR Biomedical Research Centre, University of Cambridge NHS Foundation Trust MRC Cancer Unit, Hutchison/MRC Research Centre, Cambridge, UK Department Gastroenterology, Cambridge University Hospitals, UK.</li>
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Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers
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<span class="authors-list-item "><span class="full-name">Rachel S van der Post</span><span class="citation-separator">&nbsp;et al.</span></span>
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data-ga-label="Hugo Pinheiro">Hugo Pinheiro</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal." href="#short-view-affiliation-19" ref="linksrc=author_aff">
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29
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30
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31
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32
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33
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28
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34
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35
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36
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20
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35
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37
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38
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39
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40
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1
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data-ga-label="Rebecca C Fitzgerald">Rebecca C Fitzgerald</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Cambridge NIHR Biomedical Research Centre, University of Cambridge NHS Foundation Trust MRC Cancer Unit, Hutchison/MRC Research Centre, Cambridge, UK Department Gastroenterology, Cambridge University Hospitals, UK." href="#short-view-affiliation-41" ref="linksrc=author_aff">
41
</a></sup></span>
</div>
</div>
<div class="affiliations">
<h3 class="title">
Affiliations
</h3>
<ul class="item-list">
<li data-affiliation-id="short-view-affiliation-1"
id="short-view-affiliation-1"
><sup class="key">1</sup> Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-2"
id="short-view-affiliation-2"
><sup class="key">2</sup> Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-3"
id="short-view-affiliation-3"
><sup class="key">3</sup> Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal Department of Pathology and Oncology, Medical Faculty of the University of Porto, Porto, Portugal Centro Hospitalar São João, Porto, Portugal.</li>
<li data-affiliation-id="short-view-affiliation-4"
id="short-view-affiliation-4"
><sup class="key">4</sup> Department of Biochemistry, University of Otago, Dunedin, New Zealand.</li>
<li data-affiliation-id="short-view-affiliation-5"
id="short-view-affiliation-5"
><sup class="key">5</sup> British Columbia Cancer Agency, Vancouver, British Columbia, Canada.</li>
<li data-affiliation-id="short-view-affiliation-6"
id="short-view-affiliation-6"
><sup class="key">6</sup> Department of Oncology, University of Cambridge, Cambridge, UK.</li>
<li data-affiliation-id="short-view-affiliation-7"
id="short-view-affiliation-7"
><sup class="key">7</sup> No Stomach For Cancer, Inc., Madison, Wisconsin, USA.</li>
<li data-affiliation-id="short-view-affiliation-8"
id="short-view-affiliation-8"
><sup class="key">8</sup> Department of Oesophago-Gastric Surgery, Addenbrooke&#x27;s Hospital, Cambridge, UK.</li>
<li data-affiliation-id="short-view-affiliation-9"
id="short-view-affiliation-9"
><sup class="key">9</sup> Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-10"
id="short-view-affiliation-10"
><sup class="key">10</sup> Department of Surgical Gastroenterology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.</li>
<li data-affiliation-id="short-view-affiliation-11"
id="short-view-affiliation-11"
><sup class="key">11</sup> Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.</li>
<li data-affiliation-id="short-view-affiliation-12"
id="short-view-affiliation-12"
><sup class="key">12</sup> Department of Gastroenterology, Radboud University Medical Center, Nijmegen, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-13"
id="short-view-affiliation-13"
><sup class="key">13</sup> Vinery Lane Surgery, Whangarei, New Zealand.</li>
<li data-affiliation-id="short-view-affiliation-14"
id="short-view-affiliation-14"
><sup class="key">14</sup> Division of Psychosocial Research and Epidemiology/Family Cancer Clinic, The Netherlands Cancer Institute, Amsterdam, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-15"
id="short-view-affiliation-15"
><sup class="key">15</sup> Sir Peter MacCallum Department of Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.</li>
<li data-affiliation-id="short-view-affiliation-16"
id="short-view-affiliation-16"
><sup class="key">16</sup> Department of Gastroenterology and Hepatology, Netherlands Cancer Institute/ Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-17"
id="short-view-affiliation-17"
><sup class="key">17</sup> Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.</li>
<li data-affiliation-id="short-view-affiliation-18"
id="short-view-affiliation-18"
><sup class="key">18</sup> The DeGregorio Family Foundation for Stomach and Esophageal Cancer Research, Pleasantville, New York, USA.</li>
<li data-affiliation-id="short-view-affiliation-19"
id="short-view-affiliation-19"
><sup class="key">19</sup> Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.</li>
<li data-affiliation-id="short-view-affiliation-20"
id="short-view-affiliation-20"
><sup class="key">20</sup> Division of Oncology, Stanford University School of Medicine, Stanford, California, USA.</li>
<li data-affiliation-id="short-view-affiliation-21"
id="short-view-affiliation-21"
><sup class="key">21</sup> Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-22"
id="short-view-affiliation-22"
><sup class="key">22</sup> Scientific Institute for Quality of Healthcare, Radboud University Medical Center, Nijmegen, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-23"
id="short-view-affiliation-23"
><sup class="key">23</sup> Division of Surgical Research, University of Zurich, Zurich, Suisse.</li>
<li data-affiliation-id="short-view-affiliation-24"
id="short-view-affiliation-24"
><sup class="key">24</sup> Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.</li>
<li data-affiliation-id="short-view-affiliation-25"
id="short-view-affiliation-25"
><sup class="key">25</sup> Institute of Pathology, Technische Universität, Munich, Germany.</li>
<li data-affiliation-id="short-view-affiliation-26"
id="short-view-affiliation-26"
><sup class="key">26</sup> Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-27"
id="short-view-affiliation-27"
><sup class="key">27</sup> Department of Histopathology, Cambridge University Hospitals NHS Trust, Cambridge, UK.</li>
<li data-affiliation-id="short-view-affiliation-28"
id="short-view-affiliation-28"
><sup class="key">28</sup> Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal Department of Pathology and Oncology, Medical Faculty of the University of Porto, Porto, Portugal.</li>
<li data-affiliation-id="short-view-affiliation-29"
id="short-view-affiliation-29"
><sup class="key">29</sup> NIHR Biomedical Research Unit, Nottingham Digestive Diseases Centre, Queens Medical Centre campus, Nottingham University Hospitals NHS Trust, Nottingham, UK.</li>
<li data-affiliation-id="short-view-affiliation-30"
id="short-view-affiliation-30"
><sup class="key">30</sup> Patient representative, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-31"
id="short-view-affiliation-31"
><sup class="key">31</sup> Department of Oncology, Familial Gastric Cancer Registry, Cambridge University Hospital, Cambridge, UK.</li>
<li data-affiliation-id="short-view-affiliation-32"
id="short-view-affiliation-32"
><sup class="key">32</sup> Department of General Surgery and Surgical Oncology, University of Siena, Siena, Italy.</li>
<li data-affiliation-id="short-view-affiliation-33"
id="short-view-affiliation-33"
><sup class="key">33</sup> Department of Surgical Research, Technical University Dresden, Dresden, Germany.</li>
<li data-affiliation-id="short-view-affiliation-34"
id="short-view-affiliation-34"
><sup class="key">34</sup> Cambridge University Hospital, Cambridge, UK.</li>
<li data-affiliation-id="short-view-affiliation-35"
id="short-view-affiliation-35"
><sup class="key">35</sup> Stichting CDH1, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-36"
id="short-view-affiliation-36"
><sup class="key">36</sup> Department of Medical Genetics, University of Cambridge, Cambridge, UK.</li>
<li data-affiliation-id="short-view-affiliation-37"
id="short-view-affiliation-37"
><sup class="key">37</sup> Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-38"
id="short-view-affiliation-38"
><sup class="key">38</sup> Department of Surgical Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-39"
id="short-view-affiliation-39"
><sup class="key">39</sup> Department of Surgery, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-40"
id="short-view-affiliation-40"
><sup class="key">40</sup> Radboud University Medical Center, Nijmegen, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-41"
id="short-view-affiliation-41"
><sup class="key">41</sup> Cambridge NIHR Biomedical Research Centre, University of Cambridge NHS Foundation Trust MRC Cancer Unit, Hutchison/MRC Research Centre, Cambridge, UK Department Gastroenterology, Cambridge University Hospitals, UK.</li>
</ul>
</div>
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Abstract
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<p>
Germline CDH1 mutations confer a high lifetime risk of developing diffuse gastric (DGC) and lobular breast cancer (LBC). A multidisciplinary workshop was organised to discuss genetic testing, surgery, surveillance strategies, pathology reporting and the patient's perspective on multiple aspects, including diet post gastrectomy. The updated guidelines include revised CDH1 testing criteria (taking into account first-degree and second-degree relatives): (1) families with two or more patients with gastric cancer at any age, one confirmed DGC; (2) individuals with DGC before the age of 40 and (3) families with diagnoses of both DGC and LBC (one diagnosis before the age of 50). Additionally, CDH1 testing could be considered in patients with bilateral or familial LBC before the age of 50, patients with DGC and cleft lip/palate, and those with precursor lesions for signet ring cell carcinoma. Given the high mortality associated with invasive disease, prophylactic total gastrectomy at a centre of expertise is advised for individuals with pathogenic CDH1 mutations. Breast cancer surveillance with annual breast MRI starting at age 30 for women with a CDH1 mutation is recommended. Standardised endoscopic surveillance in experienced centres is recommended for those opting not to have gastrectomy at the current time, those with CDH1 variants of uncertain significance and those that fulfil hereditary DGC criteria without germline CDH1 mutations. Expert histopathological confirmation of (early) signet ring cell carcinoma is recommended. The impact of gastrectomy and mastectomy should not be underestimated; these can have severe consequences on a psychological, physiological and metabolic level. Nutritional problems should be carefully monitored.
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<strong class="sub-title">
Keywords:
</strong>
Cancer: breast; Cancer: gastric; Clinical genetics; Diagnostics; Stomach and duodenum.
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data-pmc-id="PMC4453626"
data-figure-id="JMEDGENET2015103094F1">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-0"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c7c/4453626/9a1c23c1c441/jmedgenet-2015-103094f01.gif"
alt="Figure 1." />
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<p> Figure 1. </p>
</strong>
<div class="figure-caption-contents"><p> Algorithm for management starting from… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 1. </p>
</strong>
<div class="figure-caption-contents"><p> Algorithm for management starting from clinical hereditary diffuse gastric cancer (HDGC) testing criteria,… </p></div>
</div>
<figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 1.
</strong>
<div class="figure-caption-contents">Algorithm for management starting from clinical hereditary diffuse gastric cancer (HDGC) testing criteria, genetic testing, role of endoscopy and gastrectomy. GC, gastric cancer; DGC, diffuse gastric cancer; LBC, lobular breast cancer; MLPA, multiplex-ligation probe amplification.</div>
</figcaption>
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itemprop="contentUrl"
aria-describedby="figure-caption-1"
role="button"
data-image-width="700"
data-image-height="543"
data-image-alt="Figure 2"
data-pmc-id="PMC4453626"
data-figure-id="JMEDGENET2015103094F2">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-1"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c7c/4453626/9ee90b114c92/jmedgenet-2015-103094f02.gif"
alt="Figure 2" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="700">
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<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
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<strong class="figure-label">
<p> Figure 2 </p>
</strong>
<div class="figure-caption-contents"><p> Pale areas in gastric mucosa… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 2 </p>
</strong>
<div class="figure-caption-contents"><p> Pale areas in gastric mucosa of a patient with a germline <i> CDH1 </i> mutation… </p></div>
</div>
<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 2
</strong>
<div class="figure-caption-contents">Pale areas in gastric mucosa of a patient with a germline <i>CDH1</i> mutation harbouring signet ring cell focus during white light endoscopy (A) and narrow band imaging (B). H&amp;E stain of biopsy specimen with signet ring cells (C). Scar area after biopsy during previous endoscopy (D).</div>
</figcaption>
</figure>
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itemprop="contentUrl"
aria-describedby="figure-caption-2"
role="button"
data-image-width="747"
data-image-height="444"
data-image-alt="Figure 3"
data-pmc-id="PMC4453626"
data-figure-id="JMEDGENET2015103094F3">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-2"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c7c/4453626/4a6e2e5e221e/jmedgenet-2015-103094f03.gif"
alt="Figure 3" />
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<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 3 </p>
</strong>
<div class="figure-caption-contents"><p> Mucosal signet ring cell carcinoma… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 3 </p>
</strong>
<div class="figure-caption-contents"><p> Mucosal signet ring cell carcinoma (pT1a) H&amp;E (A), periodic acidSchiff-diastase (B), E-cadherin (C)… </p></div>
</div>
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 3
</strong>
<div class="figure-caption-contents">Mucosal signet ring cell carcinoma (pT1a) H&E (A), periodic acidSchiff-diastase (B), E-cadherin (C) and cytokeratin staining (D) (original magnifications ×200).</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
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data-slide-index="3"
data-label-slug="figure-4">
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itemprop="contentUrl"
aria-describedby="figure-caption-3"
role="button"
data-image-width="700"
data-image-height="341"
data-image-alt="Figure 4"
data-pmc-id="PMC4453626"
data-figure-id="JMEDGENET2015103094F4">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-3"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c7c/4453626/e69e1cdd9b1c/jmedgenet-2015-103094f04.gif"
alt="Figure 4" />
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<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 4 </p>
</strong>
<div class="figure-caption-contents"><p> Precursor signet ring cell lesions:… </p></div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 4 </p>
</strong>
<div class="figure-caption-contents"><p> Precursor signet ring cell lesions: pagetoid spreading of signet ring cells (A) and… </p></div>
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<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 4
</strong>
<div class="figure-caption-contents">Precursor signet ring cell lesions: pagetoid spreading of signet ring cells (A) and <i>in situ</i> signet ring cell carcinoma (B) (H&amp;E, original magnifications ×400).</div>
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Oliveira C, Ferreira P, Nabais S, Campos L, Ferreira A, Cirnes L, Alves CC, Veiga I, Fragoso M, Regateiro F, Dias LM, Moreira H, Suriano G, Machado JC, Lopes C, Castedo S, Carneiro F, Seruca R. E-Cadherin (CDH1) and p53 rather than SMAD4 and Caspase-10 germline mutations contribute to genetic predisposition in Portuguese gastric cancer patients. Eur J Cancer 2004;40:1897903. 10.1016/j.ejca.2004.04.027
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