Molecular signatures of lymph node status by intrinsic subtype: gene expression analysis of primary breast tumors from patients with and without metastatic lymph nodes
Identifieur interne : 002808 ( Main/Exploration ); précédent : 002807; suivant : 002809Molecular signatures of lymph node status by intrinsic subtype: gene expression analysis of primary breast tumors from patients with and without metastatic lymph nodes
Auteurs : Craig D. Shriver [États-Unis] ; Matthew T. Hueman [États-Unis] ; Rachel E. Ellsworth [États-Unis]Source :
- Journal of Experimental & Clinical Cancer Research : CR [ 0392-9078 ] ; 2014.
Abstract
Identification of a gene expression signature in primary breast tumors that could classify patients by lymph node status would allow patients to avoid the morbidities of surgical disruption of the lymph nodes. Attempts to identify such a signature have, to date, been unsuccessful. Because breast tumor subtypes have unique molecular characteristics and different sites of metastasis, molecular signatures for lymph node involvement may vary by subtype.
Gene expression data was generated from HG U133A 2.0 arrays for 135 node positive and 210 node negative primary breast tumors. Intrinsic subtype was assigned using the BreastPRS. Differential gene expression analysis was performed using one-way ANOVA using lymph node status as the variable with a False-discovery rate <0.05, to define significance.
Luminal A tumors were most common (51%) followed by basal-like (27%), HER2-enriched (14%) luminal B (7%) and normal-like (1%). Basal-like and luminal A tumors were less likely to have metastatic lymph nodes (35% and 37%, respectively) compared to luminal B or HER2-enriched (52% and 51%, respectively). No differentially expressed genes associated with lymph node status were detected when all tumors were considered together or within each subtype.
Gene expression patterns from the primary tumor are not able to stratify patients by lymph node status. Although the primary breast tumor may influence tumor cell dissemination, once metastatic cells enter the lymphatics, it is likely that characteristics of the lymph node microenvironment, such as establishment of a pre-metastatic niche and release of pro-survival factors, determine which cells are able to colonize. The inability to utilize molecular profiles from the primary tumor to determine lymph node status suggest that other avenues of investigation, such as how systemic factors including diminished immune response or genetic susceptibility contribute to metastasis, may be critical in the development of tools for non-surgical assessment of lymph node status with a corresponding reduction in downstream sequelae associated with disruption of the lymphatics.
Url:
DOI: 10.1186/s13046-014-0116-3
PubMed: 25551369
PubMed Central: 4322560
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Molecular signatures of lymph node status by intrinsic subtype: gene expression analysis of primary breast tumors from patients with and without metastatic lymph nodes</title><author><name sortKey="Shriver, Craig D" sort="Shriver, Craig D" uniqKey="Shriver C" first="Craig D" last="Shriver">Craig D. Shriver</name><affiliation wicri:level="2"><nlm:aff id="Aff1">Clinical Breast Care Project, Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, MD 20889 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Clinical Breast Care Project, Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Hueman, Matthew T" sort="Hueman, Matthew T" uniqKey="Hueman M" first="Matthew T" last="Hueman">Matthew T. Hueman</name><affiliation wicri:level="2"><nlm:aff id="Aff1">Clinical Breast Care Project, Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, MD 20889 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Clinical Breast Care Project, Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Ellsworth, Rachel E" sort="Ellsworth, Rachel E" uniqKey="Ellsworth R" first="Rachel E" last="Ellsworth">Rachel E. Ellsworth</name><affiliation wicri:level="2"><nlm:aff id="Aff2">Clinical Breast Care Project, Murtha Cancer Center, 620 Seventh Street, Windber, PA 15963 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Clinical Breast Care Project, Murtha Cancer Center, 620 Seventh Street, Windber</wicri:cityArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25551369</idno><idno type="pmc">4322560</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322560</idno><idno type="RBID">PMC:4322560</idno><idno type="doi">10.1186/s13046-014-0116-3</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000D62</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000D62</idno><idno type="wicri:Area/Pmc/Curation">000D61</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000D61</idno><idno type="wicri:Area/Pmc/Checkpoint">001982</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001982</idno><idno type="wicri:Area/Ncbi/Merge">006E98</idno><idno type="wicri:Area/Ncbi/Curation">006E98</idno><idno type="wicri:Area/Ncbi/Checkpoint">006E98</idno><idno type="wicri:doubleKey">0392-9078:2014:Shriver C:molecular:signatures:of</idno><idno type="wicri:Area/Main/Merge">002812</idno><idno type="wicri:Area/Main/Curation">002808</idno><idno type="wicri:Area/Main/Exploration">002808</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Molecular signatures of lymph node status by intrinsic subtype: gene expression analysis of primary breast tumors from patients with and without metastatic lymph nodes</title><author><name sortKey="Shriver, Craig D" sort="Shriver, Craig D" uniqKey="Shriver C" first="Craig D" last="Shriver">Craig D. Shriver</name><affiliation wicri:level="2"><nlm:aff id="Aff1">Clinical Breast Care Project, Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, MD 20889 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Clinical Breast Care Project, Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Hueman, Matthew T" sort="Hueman, Matthew T" uniqKey="Hueman M" first="Matthew T" last="Hueman">Matthew T. Hueman</name><affiliation wicri:level="2"><nlm:aff id="Aff1">Clinical Breast Care Project, Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, MD 20889 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Clinical Breast Care Project, Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Ellsworth, Rachel E" sort="Ellsworth, Rachel E" uniqKey="Ellsworth R" first="Rachel E" last="Ellsworth">Rachel E. Ellsworth</name><affiliation wicri:level="2"><nlm:aff id="Aff2">Clinical Breast Care Project, Murtha Cancer Center, 620 Seventh Street, Windber, PA 15963 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Clinical Breast Care Project, Murtha Cancer Center, 620 Seventh Street, Windber</wicri:cityArea></affiliation></author></analytic><series><title level="j">Journal of Experimental & Clinical Cancer Research : CR</title><idno type="ISSN">0392-9078</idno><idno type="eISSN">1756-9966</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Identification of a gene expression signature in primary breast tumors that could classify patients by lymph node status would allow patients to avoid the morbidities of surgical disruption of the lymph nodes. Attempts to identify such a signature have, to date, been unsuccessful. Because breast tumor subtypes have unique molecular characteristics and different sites of metastasis, molecular signatures for lymph node involvement may vary by subtype.</p></sec><sec><title>Methods</title><p>Gene expression data was generated from HG U133A 2.0 arrays for 135 node positive and 210 node negative primary breast tumors. Intrinsic subtype was assigned using the BreastPRS. Differential gene expression analysis was performed using one-way ANOVA using lymph node status as the variable with a False-discovery rate <0.05, to define significance.</p></sec><sec><title>Results</title><p>Luminal A tumors were most common (51%) followed by basal-like (27%), HER2-enriched (14%) luminal B (7%) and normal-like (1%). Basal-like and luminal A tumors were less likely to have metastatic lymph nodes (35% and 37%, respectively) compared to luminal B or HER2-enriched (52% and 51%, respectively). No differentially expressed genes associated with lymph node status were detected when all tumors were considered together or within each subtype.</p></sec><sec><title>Conclusions</title><p>Gene expression patterns from the primary tumor are not able to stratify patients by lymph node status. Although the primary breast tumor may influence tumor cell dissemination, once metastatic cells enter the lymphatics, it is likely that characteristics of the lymph node microenvironment, such as establishment of a pre-metastatic niche and release of pro-survival factors, determine which cells are able to colonize. The inability to utilize molecular profiles from the primary tumor to determine lymph node status suggest that other avenues of investigation, such as how systemic factors including diminished immune response or genetic susceptibility contribute to metastasis, may be critical in the development of tools for non-surgical assessment of lymph node status with a corresponding reduction in downstream sequelae associated with disruption of the lymphatics.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Sakorafas, Gh" uniqKey="Sakorafas G">GH Sakorafas</name></author><author><name sortKey="Safioleas, M" uniqKey="Safioleas M">M Safioleas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Giuliano, Ae" uniqKey="Giuliano A">AE Giuliano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fisher, B" uniqKey="Fisher B">B 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Sauer</name></author><author><name sortKey="Schneiderhan Marra, N" uniqKey="Schneiderhan Marra N">N Schneiderhan-Marra</name></author><author><name sortKey="Kazmaier, C" uniqKey="Kazmaier C">C Kazmaier</name></author><author><name sortKey="Hutzel, K" uniqKey="Hutzel K">K Hutzel</name></author><author><name sortKey="Koretz, K" uniqKey="Koretz K">K Koretz</name></author><author><name sortKey="Muche, R" uniqKey="Muche R">R Muche</name></author><author><name sortKey="Kreienberg, R" uniqKey="Kreienberg R">R Kreienberg</name></author><author><name sortKey="Joos, T" uniqKey="Joos T">T Joos</name></author><author><name sortKey="Deissler, H" uniqKey="Deissler H">H Deissler</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li><li>Pennsylvanie</li></region></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Shriver, Craig D" sort="Shriver, Craig D" uniqKey="Shriver C" first="Craig D" last="Shriver">Craig D. Shriver</name></region><name sortKey="Ellsworth, Rachel E" sort="Ellsworth, Rachel E" uniqKey="Ellsworth R" first="Rachel E" last="Ellsworth">Rachel E. Ellsworth</name><name sortKey="Hueman, Matthew T" sort="Hueman, Matthew T" uniqKey="Hueman M" first="Matthew T" last="Hueman">Matthew T. Hueman</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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