Expression of Angiopoietin-TIE System Components in Angiosarcoma
Identifieur interne : 005798 ( Ncbi/Merge ); précédent : 005797; suivant : 005799Expression of Angiopoietin-TIE System Components in Angiosarcoma
Auteurs : Darya Buehler [États-Unis] ; Patrick Rush [États-Unis] ; Jason R. Hasenstein [États-Unis] ; Stephanie R. Rice [États-Unis] ; Gholam Reza Hafez [États-Unis] ; B. Jack Longley [États-Unis] ; Kevin R. Kozak [États-Unis]Source :
- Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [ 0893-3952 ] ; 2013.
Abstract
Angiosarcoma is an aggressive malignancy of endothelial differentiation. Potential roles of the endothelial angiopoietin-tunica internal endothelial cell kinase (ANGPT-TIE) system in angiosarcoma diagnosis, pathogenesis, prognosis and treatment are undefined. To examine the expression and prognostic significance of angiopoietin-1, angiopoietin-2, TIE1 and TEK (TIE2) proteins in angiosarcoma, we immunohistochemically evaluated clinically annotated human angiosarcoma samples. Correlations of protein expression with overall survival and pathologic features were explored. The cohort included 51 patients diagnosed with angiosarcoma at age 30-86 years old (median 67). The 5-year overall survival was 45% with a median of 26 months. Moderate to strong expression of angiopoietin-1, TIE1 and TEK (TIE2) was identified in the majority of angiosarcomas and moderate to strong expression of angiopoietin-2 was observed in 42% of angiosarcomas. Increased angiopoietin-1 expression correlated with improved survival. Non-significant trends toward longer survival were also observed with increased TIE1 and TEK (TIE2) expression. Increased expression of angiopoietin-2, TIE1 and TEK (TIE2) was associated with vasoformative architecture. No differences in expression of these proteins were observed when patients were segregated by age, gender, presence or absence of metastases at diagnosis, primary tumor location, radiation association or the presence of necrosis. We conclude that components of the ANGPT-TIE system are commonly expressed in angiosarcomas. Reduced expression of these proteins is associated with non-vasoformative and clinically more aggressive lesions.
Url:
DOI: 10.1038/modpathol.2013.43
PubMed: 23558570
PubMed Central: 3706492
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<front><div type="abstract" xml:lang="en"><p id="P1">Angiosarcoma is an aggressive malignancy of endothelial differentiation. Potential roles of the endothelial angiopoietin-tunica internal endothelial cell kinase (ANGPT-TIE) system in angiosarcoma diagnosis, pathogenesis, prognosis and treatment are undefined. To examine the expression and prognostic significance of angiopoietin-1, angiopoietin-2, TIE1 and TEK (TIE2) proteins in angiosarcoma, we immunohistochemically evaluated clinically annotated human angiosarcoma samples. Correlations of protein expression with overall survival and pathologic features were explored. The cohort included 51 patients diagnosed with angiosarcoma at age 30-86 years old (median 67). The 5-year overall survival was 45% with a median of 26 months. Moderate to strong expression of angiopoietin-1, TIE1 and TEK (TIE2) was identified in the majority of angiosarcomas and moderate to strong expression of angiopoietin-2 was observed in 42% of angiosarcomas. Increased angiopoietin-1 expression correlated with improved survival. Non-significant trends toward longer survival were also observed with increased TIE1 and TEK (TIE2) expression. Increased expression of angiopoietin-2, TIE1 and TEK (TIE2) was associated with vasoformative architecture. No differences in expression of these proteins were observed when patients were segregated by age, gender, presence or absence of metastases at diagnosis, primary tumor location, radiation association or the presence of necrosis. We conclude that components of the ANGPT-TIE system are commonly expressed in angiosarcomas. Reduced expression of these proteins is associated with non-vasoformative and clinically more aggressive lesions.</p>
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</back>
</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">8806605</journal-id>
<journal-id journal-id-type="pubmed-jr-id">6644</journal-id>
<journal-id journal-id-type="nlm-ta">Mod Pathol</journal-id>
<journal-id journal-id-type="iso-abbrev">Mod. Pathol.</journal-id>
<journal-title-group><journal-title>Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc</journal-title>
</journal-title-group>
<issn pub-type="ppub">0893-3952</issn>
<issn pub-type="epub">1530-0285</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">23558570</article-id>
<article-id pub-id-type="pmc">3706492</article-id>
<article-id pub-id-type="doi">10.1038/modpathol.2013.43</article-id>
<article-id pub-id-type="manuscript">NIHMS434148</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Expression of Angiopoietin-TIE System Components in Angiosarcoma</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Buehler</surname>
<given-names>Darya</given-names>
</name>
<degrees>M.D.</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rush</surname>
<given-names>Patrick</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hasenstein</surname>
<given-names>Jason R.</given-names>
</name>
<degrees>Ph.D.</degrees>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rice</surname>
<given-names>Stephanie R.</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hafez</surname>
<given-names>Gholam Reza</given-names>
</name>
<degrees>M.D.</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Longley</surname>
<given-names>B. Jack</given-names>
</name>
<degrees>M.D.</degrees>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kozak</surname>
<given-names>Kevin R</given-names>
</name>
<degrees>M.D., Ph.D.</degrees>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Department of Pathology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin</aff>
<aff id="A2"><label>2</label>
Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin</aff>
<aff id="A3"><label>3</label>
Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin</aff>
<author-notes><corresp id="FN1">Correspondence to: Kevin R. Kozak, M.D., Ph.D., Wisconsin Institute for Medical Research, 1111 Highland Avenue Madison, WI 53705, Telephone: 608-263-8500, Fax Number: 608-262-7224, <email>kozak@humonc.wisc.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>20</day>
<month>1</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="epub"><day>05</day>
<month>4</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="ppub"><month>8</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>01</day>
<month>2</month>
<year>2014</year>
</pub-date>
<volume>26</volume>
<issue>8</issue>
<fpage>1032</fpage>
<lpage>1040</lpage>
<pmc-comment>elocation-id from pubmed: 10.1038/modpathol.2013.43</pmc-comment>
<permissions><license xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms"><license-p>Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:<ext-link ext-link-type="uri" xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms">http://www.nature.com/authors/editorial_policies/license.html#terms</ext-link>
</license-p>
</license>
</permissions>
<abstract><p id="P1">Angiosarcoma is an aggressive malignancy of endothelial differentiation. Potential roles of the endothelial angiopoietin-tunica internal endothelial cell kinase (ANGPT-TIE) system in angiosarcoma diagnosis, pathogenesis, prognosis and treatment are undefined. To examine the expression and prognostic significance of angiopoietin-1, angiopoietin-2, TIE1 and TEK (TIE2) proteins in angiosarcoma, we immunohistochemically evaluated clinically annotated human angiosarcoma samples. Correlations of protein expression with overall survival and pathologic features were explored. The cohort included 51 patients diagnosed with angiosarcoma at age 30-86 years old (median 67). The 5-year overall survival was 45% with a median of 26 months. Moderate to strong expression of angiopoietin-1, TIE1 and TEK (TIE2) was identified in the majority of angiosarcomas and moderate to strong expression of angiopoietin-2 was observed in 42% of angiosarcomas. Increased angiopoietin-1 expression correlated with improved survival. Non-significant trends toward longer survival were also observed with increased TIE1 and TEK (TIE2) expression. Increased expression of angiopoietin-2, TIE1 and TEK (TIE2) was associated with vasoformative architecture. No differences in expression of these proteins were observed when patients were segregated by age, gender, presence or absence of metastases at diagnosis, primary tumor location, radiation association or the presence of necrosis. We conclude that components of the ANGPT-TIE system are commonly expressed in angiosarcomas. Reduced expression of these proteins is associated with non-vasoformative and clinically more aggressive lesions.</p>
</abstract>
<kwd-group><kwd>Angiosarcoma</kwd>
<kwd>angiopoietin</kwd>
<kwd>sarcoma</kwd>
<kwd>TEK</kwd>
<kwd>TIE</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group><fig id="F1" orientation="portrait" position="float"><label>Figure 1</label>
<caption><title>Representative images displaying the spectrum of angiopoietin-1 and angiopoietin-2 immunoreactivity in human angiosarcomas</title>
<p>Corresponding H&E stained images are also displayed (original magnification 400x).</p>
</caption>
<graphic xlink:href="nihms434148f1"></graphic>
</fig>
<fig id="F2" orientation="portrait" position="float"><label>Figure 2</label>
<caption><title>Representative images displaying the spectrum of TIE1 and TEK (TIE2) immunoreactivity in human angiosarcomas</title>
<p>Corresponding H&E stained images are also displayed (original magnification 400x).</p>
</caption>
<graphic xlink:href="nihms434148f2"></graphic>
</fig>
<fig id="F3" orientation="portrait" position="float"><label>Figure 3</label>
<caption><title>Overall survival of angiosarcoma patients segregated by tumor expression of angiopoietin-1 (A), angiopoietin-2 (B), TIE1 (C) and TEK (TIE2) (D)</title>
</caption>
<graphic xlink:href="nihms434148f3"></graphic>
</fig>
<table-wrap id="T1" position="float" orientation="portrait"><label>Table 1</label>
<caption><p>Patient and tumor characteristics</p>
</caption>
<table frame="hsides" rules="none"><thead><tr><th align="left" rowspan="1" colspan="1"></th>
<th align="left" rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1">N (% total)</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="9" colspan="1"><italic><bold>Patient Characteristics</bold>
</italic>
</td>
<td align="left" rowspan="1" colspan="1">Age, Median (range, years)</td>
<td align="center" rowspan="1" colspan="1">67 (range, 30-86)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Gender</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> male</td>
<td align="center" rowspan="1" colspan="1">21 (41%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> female</td>
<td align="center" rowspan="1" colspan="1">30 (59%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Localized Disease</td>
<td align="center" rowspan="1" colspan="1">35 (69%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Metastatic Disease</td>
<td align="center" rowspan="1" colspan="1">16 (31%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Vital Status</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> alive</td>
<td align="center" rowspan="1" colspan="1">19 (37%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> deceased</td>
<td align="center" rowspan="1" colspan="1">32 (63%)</td>
</tr>
<tr><td align="left" rowspan="23" colspan="1"><italic><bold>Tumor Characteristics</bold>
</italic>
</td>
<td align="left" rowspan="1" colspan="1">Primary Site</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> visceral/deep soft tissue</td>
<td align="center" rowspan="1" colspan="1">20 (39%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> head and neck/cutaneous</td>
<td align="center" rowspan="1" colspan="1">20 (39%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> breast</td>
<td align="center" rowspan="1" colspan="1">8 (16%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Stewart-Treves</td>
<td align="center" rowspan="1" colspan="1">3 (6%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Radiation Associated</td>
<td align="center" rowspan="1" colspan="1">12 (24%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> breast</td>
<td align="center" rowspan="1" colspan="1">7 (58%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> bladder</td>
<td align="center" rowspan="1" colspan="1">2 (17%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> liver</td>
<td align="center" rowspan="1" colspan="1">1 (8%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> sternum</td>
<td align="center" rowspan="1" colspan="1">1 (8%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> scalp</td>
<td align="center" rowspan="1" colspan="1">1 (8%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Primary tumor size:</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Total available</td>
<td align="center" rowspan="1" colspan="1">45</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> ≤ 5 cm</td>
<td align="center" rowspan="1" colspan="1">30 (67%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> > 5 cm</td>
<td align="center" rowspan="1" colspan="1">15 (33%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Histologic pattern</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> vasoformative</td>
<td align="center" rowspan="1" colspan="1">30 (59%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> epithelioid</td>
<td align="center" rowspan="1" colspan="1">6 (12%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> spindle</td>
<td align="center" rowspan="1" colspan="1">2 (4%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> mixed</td>
<td align="center" rowspan="1" colspan="1">13 (25%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Necrosis</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> absent</td>
<td align="center" rowspan="1" colspan="1">29 (57%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> present</td>
<td align="center" rowspan="1" colspan="1">22 (43%)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"><italic><bold>Total</bold>
</italic>
</td>
<td align="left" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">51</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="T2" position="float" orientation="landscape"><label>Table 2</label>
<caption><p>Overall survival based on angiopoietin and TIE expression</p>
</caption>
<table frame="hsides" rules="none"><thead><tr><th align="center" rowspan="1" colspan="1"></th>
<th align="center" colspan="2" rowspan="1">Angiopoietin-1</th>
<th align="center" colspan="2" rowspan="1">Angiopoietin-2</th>
<th align="center" colspan="2" rowspan="1">TIE1</th>
<th align="center" colspan="2" rowspan="1">TEK (TIE2)</th>
</tr>
<tr><th align="center" rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1">0-1</th>
<th align="center" rowspan="1" colspan="1">2-3</th>
<th align="center" rowspan="1" colspan="1">0-1</th>
<th align="center" rowspan="1" colspan="1">2-3</th>
<th align="center" rowspan="1" colspan="1">0-1</th>
<th align="center" rowspan="1" colspan="1">2-3</th>
<th align="center" rowspan="1" colspan="1">0-1</th>
<th align="center" rowspan="1" colspan="1">2-3</th>
</tr>
<tr><th align="center" rowspan="1" colspan="1"></th>
<th align="center" valign="bottom" colspan="8" rowspan="1"><hr></hr>
</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1"><italic><bold>Median OS (mo)</bold>
</italic>
</td>
<td align="center" rowspan="1" colspan="1">5</td>
<td align="center" rowspan="1" colspan="1">47</td>
<td align="center" rowspan="1" colspan="1">26</td>
<td align="center" rowspan="1" colspan="1">28</td>
<td align="center" rowspan="1" colspan="1">11</td>
<td align="center" rowspan="1" colspan="1">33</td>
<td align="center" rowspan="1" colspan="1">8</td>
<td align="center" rowspan="1" colspan="1">33</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"><italic><bold>3 yr OS (%)</bold>
</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">52</td>
<td align="center" rowspan="1" colspan="1">45</td>
<td align="center" rowspan="1" colspan="1">48</td>
<td align="center" rowspan="1" colspan="1">38</td>
<td align="center" rowspan="1" colspan="1">51</td>
<td align="center" rowspan="1" colspan="1">30</td>
<td align="center" rowspan="1" colspan="1">51</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="T3" position="float" orientation="landscape"><label>Table 3</label>
<caption><p>Angiopoietin and TIE expression in patient and tumor subsets</p>
</caption>
<table frame="hsides" rules="none"><thead><tr><th align="left" rowspan="1" colspan="1"></th>
<th align="center" colspan="3" rowspan="1">Angiopoietin-1</th>
<th align="center" colspan="3" rowspan="1">Angiopoietin-2</th>
<th align="center" colspan="3" rowspan="1">TIE1</th>
<th align="center" colspan="3" rowspan="1">TEK (TIE2)</th>
</tr>
<tr><th align="left" rowspan="1" colspan="1">Age</th>
<th align="center" rowspan="1" colspan="1">0-1</th>
<th align="center" rowspan="1" colspan="1">2-3</th>
<th align="center" rowspan="1" colspan="1">P</th>
<th align="center" rowspan="1" colspan="1">0-1</th>
<th align="center" rowspan="1" colspan="1">2-3</th>
<th align="center" rowspan="1" colspan="1">P</th>
<th align="center" rowspan="1" colspan="1">0-1</th>
<th align="center" rowspan="1" colspan="1">2-3</th>
<th align="center" rowspan="1" colspan="1">P</th>
<th align="center" rowspan="1" colspan="1">0-1</th>
<th align="center" rowspan="1" colspan="1">2-3</th>
<th align="center" rowspan="1" colspan="1">P</th>
</tr>
<tr><th align="left" rowspan="1" colspan="1"></th>
<th align="center" colspan="12" valign="bottom" rowspan="1"><hr></hr>
</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1"> ≤ 67 yo</td>
<td align="center" rowspan="1" colspan="1">3</td>
<td align="center" rowspan="1" colspan="1">26</td>
<td align="center" rowspan="1" colspan="1">0.45</td>
<td align="center" rowspan="1" colspan="1">15</td>
<td align="center" rowspan="1" colspan="1">13</td>
<td align="center" rowspan="1" colspan="1">0.57</td>
<td align="center" rowspan="1" colspan="1">8</td>
<td align="center" rowspan="1" colspan="1">21</td>
<td align="center" rowspan="1" colspan="1">0.55</td>
<td align="center" rowspan="1" colspan="1">5</td>
<td align="center" rowspan="1" colspan="1">24</td>
<td align="center" rowspan="1" colspan="1">0.73</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> > 67 yo</td>
<td align="center" rowspan="1" colspan="1">4</td>
<td align="center" rowspan="1" colspan="1">18</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">14</td>
<td align="center" rowspan="1" colspan="1">8</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">8</td>
<td align="center" rowspan="1" colspan="1">14</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">5</td>
<td align="center" rowspan="1" colspan="1">17</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"><italic><bold>Gender</bold>
</italic>
</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Male</td>
<td align="center" rowspan="1" colspan="1">3</td>
<td align="center" rowspan="1" colspan="1">18</td>
<td align="center" rowspan="1" colspan="1">1.0</td>
<td align="center" rowspan="1" colspan="1">13</td>
<td align="center" rowspan="1" colspan="1">8</td>
<td align="center" rowspan="1" colspan="1">0.77</td>
<td align="center" rowspan="1" colspan="1">7</td>
<td align="center" rowspan="1" colspan="1">14</td>
<td align="center" rowspan="1" colspan="1">1.0</td>
<td align="center" rowspan="1" colspan="1">6</td>
<td align="center" rowspan="1" colspan="1">15</td>
<td align="center" rowspan="1" colspan="1">0.28</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Female</td>
<td align="center" rowspan="1" colspan="1">4</td>
<td align="center" rowspan="1" colspan="1">26</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">16</td>
<td align="center" rowspan="1" colspan="1">13</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">9</td>
<td align="center" rowspan="1" colspan="1">21</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">4</td>
<td align="center" rowspan="1" colspan="1">26</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"><italic><bold>Stage at Diagnosis</bold>
</italic>
</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Localized</td>
<td align="center" rowspan="1" colspan="1">5</td>
<td align="center" rowspan="1" colspan="1">30</td>
<td align="center" rowspan="1" colspan="1">1.0</td>
<td align="center" rowspan="1" colspan="1">19</td>
<td align="center" rowspan="1" colspan="1">15</td>
<td align="center" rowspan="1" colspan="1">0.76</td>
<td align="center" rowspan="1" colspan="1">8</td>
<td align="center" rowspan="1" colspan="1">27</td>
<td align="center" rowspan="1" colspan="1">0.10</td>
<td align="center" rowspan="1" colspan="1">6</td>
<td align="center" rowspan="1" colspan="1">29</td>
<td align="center" rowspan="1" colspan="1">0.71</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Metastatic</td>
<td align="center" rowspan="1" colspan="1">2</td>
<td align="center" rowspan="1" colspan="1">14</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">10</td>
<td align="center" rowspan="1" colspan="1">6</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">8</td>
<td align="center" rowspan="1" colspan="1">8</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">4</td>
<td align="center" rowspan="1" colspan="1">12</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"><italic><bold>Primary Site</bold>
</italic>
</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Visceral/deep soft tissue</td>
<td align="center" rowspan="1" colspan="1">5</td>
<td align="center" rowspan="1" colspan="1">15</td>
<td align="center" rowspan="1" colspan="1">0.29</td>
<td align="center" rowspan="1" colspan="1">13</td>
<td align="center" rowspan="1" colspan="1">7</td>
<td align="center" rowspan="1" colspan="1">0.15</td>
<td align="center" rowspan="1" colspan="1">10</td>
<td align="center" rowspan="1" colspan="1">10</td>
<td align="center" rowspan="1" colspan="1">0.14</td>
<td align="center" rowspan="1" colspan="1">5</td>
<td align="center" rowspan="1" colspan="1">15</td>
<td align="center" rowspan="1" colspan="1">0.45</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> HN/cutaneous</td>
<td align="center" rowspan="1" colspan="1">1</td>
<td align="center" rowspan="1" colspan="1">19</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">13</td>
<td align="center" rowspan="1" colspan="1">7</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">5</td>
<td align="center" rowspan="1" colspan="1">15</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">5</td>
<td align="center" rowspan="1" colspan="1">15</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Breast</td>
<td align="center" rowspan="1" colspan="1">1</td>
<td align="center" rowspan="1" colspan="1">7</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">3</td>
<td align="center" rowspan="1" colspan="1">4</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">1</td>
<td align="center" rowspan="1" colspan="1">7</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">8</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Stewart-Treves</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">3</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">3</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">3</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">3</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"><italic><bold>Radiation Associated</bold>
</italic>
</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Yes</td>
<td align="center" rowspan="1" colspan="1">2</td>
<td align="center" rowspan="1" colspan="1">10</td>
<td align="center" rowspan="1" colspan="1">0.66</td>
<td align="center" rowspan="1" colspan="1">6</td>
<td align="center" rowspan="1" colspan="1">5</td>
<td align="center" rowspan="1" colspan="1">1.0</td>
<td align="center" rowspan="1" colspan="1">3</td>
<td align="center" rowspan="1" colspan="1">9</td>
<td align="center" rowspan="1" colspan="1">0.73</td>
<td align="center" rowspan="1" colspan="1">2</td>
<td align="center" rowspan="1" colspan="1">10</td>
<td align="center" rowspan="1" colspan="1">1.0</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> No</td>
<td align="center" rowspan="1" colspan="1">5</td>
<td align="center" rowspan="1" colspan="1">34</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">23</td>
<td align="center" rowspan="1" colspan="1">16</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">13</td>
<td align="center" rowspan="1" colspan="1">26</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">8</td>
<td align="center" rowspan="1" colspan="1">31</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"><italic><bold>Tumor Size</bold>
</italic>
</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> ≤ 5 cm</td>
<td align="center" rowspan="1" colspan="1">5</td>
<td align="center" rowspan="1" colspan="1">25</td>
<td align="center" rowspan="1" colspan="1">0.69</td>
<td align="center" rowspan="1" colspan="1">19</td>
<td align="center" rowspan="1" colspan="1">10</td>
<td align="center" rowspan="1" colspan="1">0.25</td>
<td align="center" rowspan="1" colspan="1">8</td>
<td align="center" rowspan="1" colspan="1">22</td>
<td align="center" rowspan="1" colspan="1">0.54</td>
<td align="center" rowspan="1" colspan="1">4</td>
<td align="center" rowspan="1" colspan="1">26</td>
<td align="center" rowspan="1" colspan="1">0.28</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> > 5 cm</td>
<td align="center" rowspan="1" colspan="1">2</td>
<td align="center" rowspan="1" colspan="1">19</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">10</td>
<td align="center" rowspan="1" colspan="1">11</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">8</td>
<td align="center" rowspan="1" colspan="1">13</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">6</td>
<td align="center" rowspan="1" colspan="1">15</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"><italic><bold>Histologic Pattern</bold>
</italic>
</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Vasoformative</td>
<td align="center" rowspan="1" colspan="1">2</td>
<td align="center" rowspan="1" colspan="1">28</td>
<td align="center" rowspan="1" colspan="1">0.11</td>
<td align="center" rowspan="1" colspan="1">13</td>
<td align="center" rowspan="1" colspan="1">16</td>
<td align="center" rowspan="1" colspan="1"><bold>0.04</bold>
</td>
<td align="center" rowspan="1" colspan="1">3</td>
<td align="center" rowspan="1" colspan="1">27</td>
<td align="center" rowspan="1" colspan="1"><bold>0.0001</bold>
</td>
<td align="center" rowspan="1" colspan="1">2</td>
<td align="center" rowspan="1" colspan="1">28</td>
<td align="center" rowspan="1" colspan="1"><bold>0.01</bold>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Non-vasoformative</td>
<td align="center" rowspan="1" colspan="1">5</td>
<td align="center" rowspan="1" colspan="1">16</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">16</td>
<td align="center" rowspan="1" colspan="1">5</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">13</td>
<td align="center" rowspan="1" colspan="1">8</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">8</td>
<td align="center" rowspan="1" colspan="1">13</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"><italic><bold>Necrosis</bold>
</italic>
</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Present</td>
<td align="center" rowspan="1" colspan="1">5</td>
<td align="center" rowspan="1" colspan="1">17</td>
<td align="center" rowspan="1" colspan="1">0.22</td>
<td align="center" rowspan="1" colspan="1">12</td>
<td align="center" rowspan="1" colspan="1">10</td>
<td align="center" rowspan="1" colspan="1">0.78</td>
<td align="center" rowspan="1" colspan="1">10</td>
<td align="center" rowspan="1" colspan="1">12</td>
<td align="center" rowspan="1" colspan="1">0.07</td>
<td align="center" rowspan="1" colspan="1">6</td>
<td align="center" rowspan="1" colspan="1">16</td>
<td align="center" rowspan="1" colspan="1">0.30</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Absent</td>
<td align="center" rowspan="1" colspan="1">2</td>
<td align="center" rowspan="1" colspan="1">27</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">17</td>
<td align="center" rowspan="1" colspan="1">11</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">6</td>
<td align="center" rowspan="1" colspan="1">23</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">4</td>
<td align="center" rowspan="1" colspan="1">25</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
</tbody>
</table>
</table-wrap>
</floats-group>
</pmc>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Wisconsin</li>
</region>
</list>
<tree><country name="États-Unis"><region name="Wisconsin"><name sortKey="Buehler, Darya" sort="Buehler, Darya" uniqKey="Buehler D" first="Darya" last="Buehler">Darya Buehler</name>
</region>
<name sortKey="Hafez, Gholam Reza" sort="Hafez, Gholam Reza" uniqKey="Hafez G" first="Gholam Reza" last="Hafez">Gholam Reza Hafez</name>
<name sortKey="Hasenstein, Jason R" sort="Hasenstein, Jason R" uniqKey="Hasenstein J" first="Jason R." last="Hasenstein">Jason R. Hasenstein</name>
<name sortKey="Kozak, Kevin R" sort="Kozak, Kevin R" uniqKey="Kozak K" first="Kevin R" last="Kozak">Kevin R. Kozak</name>
<name sortKey="Longley, B Jack" sort="Longley, B Jack" uniqKey="Longley B" first="B. Jack" last="Longley">B. Jack Longley</name>
<name sortKey="Rice, Stephanie R" sort="Rice, Stephanie R" uniqKey="Rice S" first="Stephanie R." last="Rice">Stephanie R. Rice</name>
<name sortKey="Rush, Patrick" sort="Rush, Patrick" uniqKey="Rush P" first="Patrick" last="Rush">Patrick Rush</name>
</country>
</tree>
</affiliations>
</record>
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