Reliable Entity Subtyping in Non-small Cell Lung Cancer by Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry on Formalin-fixed Paraffin-embedded Tissue Specimens.
Identifieur interne : 000101 ( Main/Exploration ); précédent : 000100; suivant : 000102Reliable Entity Subtyping in Non-small Cell Lung Cancer by Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry on Formalin-fixed Paraffin-embedded Tissue Specimens.
Auteurs : Mark Kriegsmann [Allemagne] ; Rita Casadonte [Allemagne] ; Jörg Kriegsmann [Allemagne] ; Hendrik Dienemann [Allemagne] ; Peter Schirmacher [Allemagne] ; Jan Hendrik Kobarg [Allemagne] ; Kristina Schwamborn [Allemagne] ; Albrecht Stenzinger ; Arne Warth ; Wilko Weichert [Allemagne]Source :
- Molecular & cellular proteomics : MCP [ 1535-9484 ] ; 2016.
Abstract
Histopathological subtyping of non-small cell lung cancer (NSCLC) into adenocarcinoma (ADC), and squamous cell carcinoma (SqCC) is of utmost relevance for treatment stratification. However, current immunohistochemistry (IHC) based typing approaches on biopsies are imperfect, therefore novel analytical methods for reliable subtyping are needed. We analyzed formalin-fixed paraffin-embedded tissue cores of NSCLC by Matrix-assisted laser desorption/ionization (MALDI) imaging on tissue microarrays to identify and validate discriminating MALDI imaging profiles for NSCLC subtyping. 110 ADC and 98 SqCC were used to train a Linear Discriminant Analysis (LDA) model. Results were validated on a separate set of 58 ADC and 60 SqCC. Selected differentially expressed proteins were identified by tandem mass spectrometry and validated by IHC. The LDA classification model incorporated 339 m/z values. In the validation cohort, in 117 cases (99.1%) MALDI classification on tissue cores was in accordance with the pathological diagnosis made on resection specimen. Overall, three cases in the combined cohorts were discordant, after reevaluation two were initially misclassified by pathology whereas one was classified incorrectly by MALDI. Identification of differentially expressed peptides detected well-known IHC discriminators (CK5, CK7), but also less well known differentially expressed proteins (CK15, HSP27). In conclusion, MALDI imaging on NSCLC tissue cores as small biopsy equivalents is capable to discriminate lung ADC and SqCC with a very high accuracy. In addition, replacing multislide IHC by an one-slide MALDI approach may also save tissue for subsequent predictive molecular testing. We therefore advocate to pursue routine diagnostic implementation strategies for MALDI imaging in solid tumor typing.
DOI: 10.1074/mcp.M115.057513
PubMed: 27473201
Affiliations:
- Allemagne
- Bade-Wurtemberg, Bavière, Brême (Land), District de Haute-Bavière, District de Karlsruhe
- Brême, Heidelberg, Munich
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¶Center for Histology, Cytology and Molecular Diagnostics, 54296 Trier, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>§Proteopath GmbH, 54296 Trier, Germany; ¶Center for Histology, Cytology and Molecular Diagnostics, 54296 Trier</wicri:regionArea><wicri:noRegion>54296 Trier</wicri:noRegion><wicri:noRegion>54296 Trier</wicri:noRegion><wicri:noRegion>54296 Trier</wicri:noRegion></affiliation></author><author><name sortKey="Dienemann, Hendrik" sort="Dienemann, Hendrik" uniqKey="Dienemann H" first="Hendrik" last="Dienemann">Hendrik Dienemann</name><affiliation wicri:level="3"><nlm:affiliation>‖Department of Thoracic Surgery, Thoraxklinik at Heidelberg University, 69126 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>‖Department of Thoracic Surgery, Thoraxklinik at Heidelberg University, 69126 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Schirmacher, Peter" sort="Schirmacher, Peter" uniqKey="Schirmacher P" first="Peter" last="Schirmacher">Peter Schirmacher</name><affiliation wicri:level="3"><nlm:affiliation>From the ‡Institute of Pathology, University Heidelberg, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>From the ‡Institute of Pathology, University Heidelberg, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Hendrik Kobarg, Jan" sort="Hendrik Kobarg, Jan" uniqKey="Hendrik Kobarg J" first="Jan" last="Hendrik Kobarg">Jan Hendrik Kobarg</name><affiliation wicri:level="3"><nlm:affiliation>**SCiLS GmbH, 28359 Bremen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>**SCiLS GmbH, 28359 Bremen</wicri:regionArea><placeName><region type="land" nuts="3">Brême (Land)</region><settlement type="city">Brême</settlement></placeName></affiliation></author><author><name sortKey="Schwamborn, Kristina" sort="Schwamborn, Kristina" uniqKey="Schwamborn K" first="Kristina" last="Schwamborn">Kristina Schwamborn</name><affiliation wicri:level="3"><nlm:affiliation>‡‡Institute of Pathology, Technical University Munich (TUM), 81675 Munich, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>‡‡Institute of Pathology, Technical University Munich (TUM), 81675 Munich</wicri:regionArea><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName></affiliation></author><author><name sortKey="Stenzinger, Albrecht" sort="Stenzinger, Albrecht" uniqKey="Stenzinger A" first="Albrecht" last="Stenzinger">Albrecht Stenzinger</name><affiliation><nlm:affiliation>From the ‡Institute of Pathology, University Heidelberg, 69120 Heidelberg, Germany; §§German Cancer Consortium (DKTK).</nlm:affiliation><wicri:noCountry code="subField">Germany; §§German Cancer Consortium (DKTK)</wicri:noCountry></affiliation></author><author><name sortKey="Warth, Arne" sort="Warth, Arne" uniqKey="Warth A" first="Arne" last="Warth">Arne Warth</name><affiliation><nlm:affiliation>From the ‡Institute of Pathology, University Heidelberg, 69120 Heidelberg, Germany; ¶¶Translational Lung Research Centre Heidelberg, Member of the German Centre for Lung Research.</nlm:affiliation><wicri:noCountry code="subField">Member of the German Centre for Lung Research</wicri:noCountry></affiliation></author><author><name sortKey="Weichert, Wilko" sort="Weichert, Wilko" uniqKey="Weichert W" first="Wilko" last="Weichert">Wilko Weichert</name><affiliation wicri:level="3"><nlm:affiliation>From the ‡Institute of Pathology, University Heidelberg, 69120 Heidelberg, Germany; ‡‡Institute of Pathology, Technical University Munich (TUM), 81675 Munich, Germany; §§German Cancer Consortium (DKTK); ‖‖National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>From the ‡Institute of Pathology, University Heidelberg, 69120 Heidelberg, Germany; ‡‡Institute of Pathology, Technical University Munich (TUM), 81675 Munich, Germany; §§German Cancer Consortium (DKTK); ‖‖National Center for Tumor Diseases (NCT), 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27473201</idno><idno type="pmid">27473201</idno><idno type="doi">10.1074/mcp.M115.057513</idno><idno type="wicri:Area/PubMed/Corpus">000080</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000080</idno><idno type="wicri:Area/PubMed/Curation">000080</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000080</idno><idno type="wicri:Area/PubMed/Checkpoint">000080</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000080</idno><idno type="wicri:Area/Ncbi/Merge">000961</idno><idno type="wicri:Area/Ncbi/Curation">000961</idno><idno type="wicri:Area/Ncbi/Checkpoint">000961</idno><idno type="wicri:Area/Main/Merge">000101</idno><idno type="wicri:Area/Main/Curation">000101</idno><idno type="wicri:Area/Main/Exploration">000101</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Reliable Entity Subtyping in Non-small Cell Lung Cancer by Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry on Formalin-fixed Paraffin-embedded Tissue Specimens.</title><author><name sortKey="Kriegsmann, Mark" sort="Kriegsmann, Mark" uniqKey="Kriegsmann M" first="Mark" last="Kriegsmann">Mark Kriegsmann</name><affiliation wicri:level="3"><nlm:affiliation>From the ‡Institute of Pathology, University Heidelberg, 69120 Heidelberg, Germany; mark.kriegsmann@med.uni-heidelberg.de.</nlm:affiliation><country wicri:rule="url">Allemagne</country><wicri:regionArea>From the ‡Institute of Pathology, University Heidelberg, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Casadonte, Rita" sort="Casadonte, Rita" uniqKey="Casadonte R" first="Rita" last="Casadonte">Rita Casadonte</name><affiliation wicri:level="1"><nlm:affiliation>§Proteopath GmbH, 54296 Trier, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>§Proteopath GmbH, 54296 Trier</wicri:regionArea><wicri:noRegion>54296 Trier</wicri:noRegion><wicri:noRegion>54296 Trier</wicri:noRegion><wicri:noRegion>54296 Trier</wicri:noRegion></affiliation></author><author><name sortKey="Kriegsmann, Jorg" sort="Kriegsmann, Jorg" uniqKey="Kriegsmann J" first="Jörg" last="Kriegsmann">Jörg Kriegsmann</name><affiliation wicri:level="1"><nlm:affiliation>§Proteopath GmbH, 54296 Trier, Germany; ¶Center for Histology, Cytology and Molecular Diagnostics, 54296 Trier, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>§Proteopath GmbH, 54296 Trier, Germany; ¶Center for Histology, Cytology and Molecular Diagnostics, 54296 Trier</wicri:regionArea><wicri:noRegion>54296 Trier</wicri:noRegion><wicri:noRegion>54296 Trier</wicri:noRegion><wicri:noRegion>54296 Trier</wicri:noRegion></affiliation></author><author><name sortKey="Dienemann, Hendrik" sort="Dienemann, Hendrik" uniqKey="Dienemann H" first="Hendrik" last="Dienemann">Hendrik Dienemann</name><affiliation wicri:level="3"><nlm:affiliation>‖Department of Thoracic Surgery, Thoraxklinik at Heidelberg University, 69126 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>‖Department of Thoracic Surgery, Thoraxklinik at Heidelberg University, 69126 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Schirmacher, Peter" sort="Schirmacher, Peter" uniqKey="Schirmacher P" first="Peter" last="Schirmacher">Peter Schirmacher</name><affiliation wicri:level="3"><nlm:affiliation>From the ‡Institute of Pathology, University Heidelberg, 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>From the ‡Institute of Pathology, University Heidelberg, 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Hendrik Kobarg, Jan" sort="Hendrik Kobarg, Jan" uniqKey="Hendrik Kobarg J" first="Jan" last="Hendrik Kobarg">Jan Hendrik Kobarg</name><affiliation wicri:level="3"><nlm:affiliation>**SCiLS GmbH, 28359 Bremen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>**SCiLS GmbH, 28359 Bremen</wicri:regionArea><placeName><region type="land" nuts="3">Brême (Land)</region><settlement type="city">Brême</settlement></placeName></affiliation></author><author><name sortKey="Schwamborn, Kristina" sort="Schwamborn, Kristina" uniqKey="Schwamborn K" first="Kristina" last="Schwamborn">Kristina Schwamborn</name><affiliation wicri:level="3"><nlm:affiliation>‡‡Institute of Pathology, Technical University Munich (TUM), 81675 Munich, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>‡‡Institute of Pathology, Technical University Munich (TUM), 81675 Munich</wicri:regionArea><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName></affiliation></author><author><name sortKey="Stenzinger, Albrecht" sort="Stenzinger, Albrecht" uniqKey="Stenzinger A" first="Albrecht" last="Stenzinger">Albrecht Stenzinger</name><affiliation><nlm:affiliation>From the ‡Institute of Pathology, University Heidelberg, 69120 Heidelberg, Germany; §§German Cancer Consortium (DKTK).</nlm:affiliation><wicri:noCountry code="subField">Germany; §§German Cancer Consortium (DKTK)</wicri:noCountry></affiliation></author><author><name sortKey="Warth, Arne" sort="Warth, Arne" uniqKey="Warth A" first="Arne" last="Warth">Arne Warth</name><affiliation><nlm:affiliation>From the ‡Institute of Pathology, University Heidelberg, 69120 Heidelberg, Germany; ¶¶Translational Lung Research Centre Heidelberg, Member of the German Centre for Lung Research.</nlm:affiliation><wicri:noCountry code="subField">Member of the German Centre for Lung Research</wicri:noCountry></affiliation></author><author><name sortKey="Weichert, Wilko" sort="Weichert, Wilko" uniqKey="Weichert W" first="Wilko" last="Weichert">Wilko Weichert</name><affiliation wicri:level="3"><nlm:affiliation>From the ‡Institute of Pathology, University Heidelberg, 69120 Heidelberg, Germany; ‡‡Institute of Pathology, Technical University Munich (TUM), 81675 Munich, Germany; §§German Cancer Consortium (DKTK); ‖‖National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>From the ‡Institute of Pathology, University Heidelberg, 69120 Heidelberg, Germany; ‡‡Institute of Pathology, Technical University Munich (TUM), 81675 Munich, Germany; §§German Cancer Consortium (DKTK); ‖‖National Center for Tumor Diseases (NCT), 69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author></analytic><series><title level="j">Molecular & cellular proteomics : MCP</title><idno type="eISSN">1535-9484</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Histopathological subtyping of non-small cell lung cancer (NSCLC) into adenocarcinoma (ADC), and squamous cell carcinoma (SqCC) is of utmost relevance for treatment stratification. However, current immunohistochemistry (IHC) based typing approaches on biopsies are imperfect, therefore novel analytical methods for reliable subtyping are needed. We analyzed formalin-fixed paraffin-embedded tissue cores of NSCLC by Matrix-assisted laser desorption/ionization (MALDI) imaging on tissue microarrays to identify and validate discriminating MALDI imaging profiles for NSCLC subtyping. 110 ADC and 98 SqCC were used to train a Linear Discriminant Analysis (LDA) model. Results were validated on a separate set of 58 ADC and 60 SqCC. Selected differentially expressed proteins were identified by tandem mass spectrometry and validated by IHC. The LDA classification model incorporated 339 m/z values. In the validation cohort, in 117 cases (99.1%) MALDI classification on tissue cores was in accordance with the pathological diagnosis made on resection specimen. Overall, three cases in the combined cohorts were discordant, after reevaluation two were initially misclassified by pathology whereas one was classified incorrectly by MALDI. Identification of differentially expressed peptides detected well-known IHC discriminators (CK5, CK7), but also less well known differentially expressed proteins (CK15, HSP27). In conclusion, MALDI imaging on NSCLC tissue cores as small biopsy equivalents is capable to discriminate lung ADC and SqCC with a very high accuracy. In addition, replacing multislide IHC by an one-slide MALDI approach may also save tissue for subsequent predictive molecular testing. We therefore advocate to pursue routine diagnostic implementation strategies for MALDI imaging in solid tumor typing.</div></front></TEI><affiliations><list><country><li>Allemagne</li></country><region><li>Bade-Wurtemberg</li><li>Bavière</li><li>Brême (Land)</li><li>District de Haute-Bavière</li><li>District de Karlsruhe</li></region><settlement><li>Brême</li><li>Heidelberg</li><li>Munich</li></settlement></list><tree><noCountry><name sortKey="Stenzinger, Albrecht" sort="Stenzinger, Albrecht" uniqKey="Stenzinger A" first="Albrecht" last="Stenzinger">Albrecht Stenzinger</name><name sortKey="Warth, Arne" sort="Warth, Arne" uniqKey="Warth A" first="Arne" last="Warth">Arne Warth</name></noCountry><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Kriegsmann, Mark" sort="Kriegsmann, Mark" uniqKey="Kriegsmann M" first="Mark" last="Kriegsmann">Mark Kriegsmann</name></region><name sortKey="Casadonte, Rita" sort="Casadonte, Rita" uniqKey="Casadonte R" first="Rita" last="Casadonte">Rita Casadonte</name><name sortKey="Dienemann, Hendrik" sort="Dienemann, Hendrik" uniqKey="Dienemann H" first="Hendrik" last="Dienemann">Hendrik Dienemann</name><name sortKey="Hendrik Kobarg, Jan" sort="Hendrik Kobarg, Jan" uniqKey="Hendrik Kobarg J" first="Jan" last="Hendrik Kobarg">Jan Hendrik Kobarg</name><name sortKey="Kriegsmann, Jorg" sort="Kriegsmann, Jorg" uniqKey="Kriegsmann J" first="Jörg" last="Kriegsmann">Jörg Kriegsmann</name><name sortKey="Schirmacher, Peter" sort="Schirmacher, Peter" uniqKey="Schirmacher P" first="Peter" last="Schirmacher">Peter Schirmacher</name><name sortKey="Schwamborn, Kristina" sort="Schwamborn, Kristina" uniqKey="Schwamborn K" first="Kristina" last="Schwamborn">Kristina Schwamborn</name><name sortKey="Weichert, Wilko" sort="Weichert, Wilko" uniqKey="Weichert W" first="Wilko" last="Weichert">Wilko Weichert</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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