HER2 in situ hybridization in breast cancer: clinical implications of polysomy 17 and genetic heterogeneity.
Identifieur interne : 003865 ( Main/Exploration ); précédent : 003864; suivant : 003866HER2 in situ hybridization in breast cancer: clinical implications of polysomy 17 and genetic heterogeneity.
Auteurs : Wedad M. Hanna [Canada] ; Josef Rüschoff [Allemagne] ; Michael Bilous [Australie] ; Renata A. Coudry [Brésil] ; Mitch Dowsett [Royaume-Uni] ; Robert Y. Osamura [Japon] ; Frédérique Penault-Llorca [France] ; Marc Van De Vijver [Pays-Bas] ; Giuseppe Viale [Italie]Source :
- Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [ 1530-0285 ] ; 2014.
Descripteurs français
- KwdFr :
- Amplification de gène, Anticorps monoclonaux humanisés (usage thérapeutique), Antinéoplasiques (usage thérapeutique), Centromère, Chromosomes humains de la paire 17, Dosage génique, Femelle, Humains, Hybridation in situ, Hétérogénéité génétique, Inhibiteurs de protéines kinases (usage thérapeutique), Médecine individualisée, Phénotype, Prédisposition génétique à une maladie, Récepteur ErbB-2 (antagonistes et inhibiteurs), Récepteur ErbB-2 (génétique), Récepteur ErbB-2 (métabolisme), Sélection de patients, Trastuzumab, Tumeurs du sein (anatomopathologie), Tumeurs du sein (enzymologie), Tumeurs du sein (génétique), Tumeurs du sein (traitement médicamenteux), Valeur prédictive des tests.
- MESH :
- anatomopathologie : Tumeurs du sein.
- antagonistes et inhibiteurs : Récepteur ErbB-2.
- enzymologie : Tumeurs du sein.
- génétique : Récepteur ErbB-2, Tumeurs du sein.
- métabolisme : Récepteur ErbB-2.
- traitement médicamenteux : Tumeurs du sein.
- usage thérapeutique : Anticorps monoclonaux humanisés, Antinéoplasiques, Inhibiteurs de protéines kinases.
- Amplification de gène, Centromère, Chromosomes humains de la paire 17, Dosage génique, Femelle, Humains, Hybridation in situ, Hétérogénéité génétique, Médecine individualisée, Phénotype, Prédisposition génétique à une maladie, Sélection de patients, Trastuzumab, Valeur prédictive des tests.
English descriptors
- KwdEn :
- Antibodies, Monoclonal, Humanized (therapeutic use), Antineoplastic Agents (therapeutic use), Breast Neoplasms (drug therapy), Breast Neoplasms (enzymology), Breast Neoplasms (genetics), Breast Neoplasms (pathology), Centromere, Chromosomes, Human, Pair 17, Female, Gene Amplification, Gene Dosage, Genetic Heterogeneity, Genetic Predisposition to Disease, Humans, In Situ Hybridization, Patient Selection, Phenotype, Precision Medicine, Predictive Value of Tests, Protein Kinase Inhibitors (therapeutic use), Receptor, ErbB-2 (antagonists & inhibitors), Receptor, ErbB-2 (genetics), Receptor, ErbB-2 (metabolism), Trastuzumab.
- MESH :
- chemical , antagonists & inhibitors : Receptor, ErbB-2.
- chemical , genetics : Receptor, ErbB-2.
- chemical , metabolism : Receptor, ErbB-2.
- chemical , therapeutic use : Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Protein Kinase Inhibitors.
- drug therapy : Breast Neoplasms.
- enzymology : Breast Neoplasms.
- genetics : Breast Neoplasms.
- pathology : Breast Neoplasms.
- Centromere, Chromosomes, Human, Pair 17, Female, Gene Amplification, Gene Dosage, Genetic Heterogeneity, Genetic Predisposition to Disease, Humans, In Situ Hybridization, Patient Selection, Phenotype, Precision Medicine, Predictive Value of Tests, Trastuzumab.
Abstract
Trastuzumab-containing therapy is a standard of care for patients with HER2+ breast cancer. HER2 status is routinely assigned using in situ hybridization to assess HER2 gene amplification, but interpretation of in situ hybridization results may be challenging in tumors with chromosome 17 polysomy or intratumoral genetic heterogeneity. Apparent chromosome 17 polysomy, defined by increased chromosome enumeration probe 17 (CEP17) signal number, is a common genetic aberration in breast cancer and represents an alternative mechanism for increasing HER2 copy number. Some studies have linked elevated CEP17 count ('polysomy') with adverse clinicopathologic features and HER2 overexpression, although there are numerous discrepancies in the literature. There is evidence that elevated CEP17 ('polysomy') count might account for trastuzumab response in tumors with normal HER2:CEP17 ratios. Nonetheless, recent studies establish that apparent 'polysomy' (CEP17 increase) is usually related to focal pericentromeric gains rather than true polysomy. Assigning HER2 status may also be complex where multiple cell subclones with distinct HER2 amplification characteristics coexist within the same tumor. Such genetic heterogeneity affects up to 40% of breast cancers when assessed according to a College of American Pathologists guideline, although other definitions have been proposed. Recent data have associated heterogeneity with unfavorable clinicopathologic variables and poor prognosis. Genetically heterogeneous tumors harboring HER2-amplified subclones have the potential to benefit from trastuzumab, but this has yet to be evaluated in clinical studies. In this review, we discuss the implications of apparent polysomy 17 and genetic heterogeneity for assigning HER2 status in clinical practice. Among our recommendations, we support the use of mean HER2 copy number rather than HER2:CEP17 ratio to define HER2 positivity in cases where coamplification of the centromere might mask HER2 amplification. We also highlight a need to harmonize in situ hybridization scoring methodology to support accurate HER2 status determination, particularly where there is evidence of heterogeneity.
DOI: 10.1038/modpathol.2013.103
PubMed: 23807776
Affiliations:
- Allemagne, Australie, Brésil, Canada, France, Italie, Japon, Pays-Bas, Royaume-Uni
- Angleterre, Auvergne (région administrative), Auvergne-Rhône-Alpes, District de Kassel, Grand Londres, Hesse (Land), Hollande-Septentrionale, Lombardie, Ontario, Région de Kantō, État de São Paulo
- Amsterdam, Cassel (Hesse), Clermont-Ferrand, Londres, Milan, São Paulo, Tokyo, Toronto
- Université d'Amsterdam, Université de Toronto
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Le document en format XML
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Hanna</name><affiliation wicri:level="4"><nlm:affiliation>Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Ruschoff, Josef" sort="Ruschoff, Josef" uniqKey="Ruschoff J" first="Josef" last="Rüschoff">Josef Rüschoff</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Pathology Nordhessen, Kassel, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Pathology Nordhessen, Kassel</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Kassel</region><settlement type="city">Cassel (Hesse)</settlement></placeName></affiliation></author><author><name sortKey="Bilous, Michael" sort="Bilous, Michael" uniqKey="Bilous M" first="Michael" last="Bilous">Michael Bilous</name><affiliation wicri:level="1"><nlm:affiliation>Healthscope Pathology, Norwest Private Hospital, Bella Vista, NSW, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Healthscope Pathology, Norwest Private Hospital, Bella Vista, NSW</wicri:regionArea><wicri:noRegion>NSW</wicri:noRegion></affiliation></author><author><name sortKey="Coudry, Renata A" sort="Coudry, Renata A" uniqKey="Coudry R" first="Renata A" last="Coudry">Renata A. Coudry</name><affiliation wicri:level="3"><nlm:affiliation>State of São Paulo Cancer Institute (ICESP), São Paulo, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>State of São Paulo Cancer Institute (ICESP), São Paulo</wicri:regionArea><placeName><settlement type="city">São Paulo</settlement><region type="state">État de São Paulo</region></placeName></affiliation></author><author><name sortKey="Dowsett, Mitch" sort="Dowsett, Mitch" uniqKey="Dowsett M" first="Mitch" last="Dowsett">Mitch Dowsett</name><affiliation wicri:level="3"><nlm:affiliation>Royal Marsden Hospital, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Royal Marsden Hospital, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Osamura, Robert Y" sort="Osamura, Robert Y" uniqKey="Osamura R" first="Robert Y" last="Osamura">Robert Y. Osamura</name><affiliation wicri:level="3"><nlm:affiliation>International University of Health and Welfare (IUHW), Center for Diagnostic Pathology, IUHW Mita Hospital, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>International University of Health and Welfare (IUHW), Center for Diagnostic Pathology, IUHW Mita Hospital, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Penault Llorca, Frederique" sort="Penault Llorca, Frederique" uniqKey="Penault Llorca F" first="Frédérique" last="Penault-Llorca">Frédérique Penault-Llorca</name><affiliation wicri:level="3"><nlm:affiliation>Centre Jean Perrin and University of Auvergne, EA 4233, Clermont-Ferrand, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre Jean Perrin and University of Auvergne, EA 4233, Clermont-Ferrand</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Auvergne (région administrative)</region><settlement type="city">Clermont-Ferrand</settlement></placeName></affiliation></author><author><name sortKey="Van De Vijver, Marc" sort="Van De Vijver, Marc" uniqKey="Van De Vijver M" first="Marc" last="Van De Vijver">Marc Van De Vijver</name><affiliation wicri:level="4"><nlm:affiliation>The Academic Medical Center (AMC), The University of Amsterdam, Amsterdam, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>The Academic Medical Center (AMC), The University of Amsterdam, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region><settlement type="city">Amsterdam</settlement></placeName><orgName type="university">Université d'Amsterdam</orgName></affiliation></author><author><name sortKey="Viale, Giuseppe" sort="Viale, Giuseppe" uniqKey="Viale G" first="Giuseppe" last="Viale">Giuseppe Viale</name><affiliation wicri:level="3"><nlm:affiliation>University of Milan and European Institute of Oncology, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>University of Milan and European Institute of Oncology, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author></analytic><series><title level="j">Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc</title><idno type="eISSN">1530-0285</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antibodies, Monoclonal, Humanized (therapeutic use)</term><term>Antineoplastic Agents (therapeutic use)</term><term>Breast Neoplasms (drug therapy)</term><term>Breast Neoplasms (enzymology)</term><term>Breast Neoplasms (genetics)</term><term>Breast Neoplasms (pathology)</term><term>Centromere</term><term>Chromosomes, Human, Pair 17</term><term>Female</term><term>Gene Amplification</term><term>Gene Dosage</term><term>Genetic Heterogeneity</term><term>Genetic Predisposition to Disease</term><term>Humans</term><term>In Situ Hybridization</term><term>Patient Selection</term><term>Phenotype</term><term>Precision Medicine</term><term>Predictive Value of Tests</term><term>Protein Kinase Inhibitors (therapeutic use)</term><term>Receptor, ErbB-2 (antagonists & inhibitors)</term><term>Receptor, ErbB-2 (genetics)</term><term>Receptor, ErbB-2 (metabolism)</term><term>Trastuzumab</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Amplification de gène</term><term>Anticorps monoclonaux humanisés (usage thérapeutique)</term><term>Antinéoplasiques (usage thérapeutique)</term><term>Centromère</term><term>Chromosomes humains de la paire 17</term><term>Dosage génique</term><term>Femelle</term><term>Humains</term><term>Hybridation in situ</term><term>Hétérogénéité génétique</term><term>Inhibiteurs de protéines kinases (usage thérapeutique)</term><term>Médecine individualisée</term><term>Phénotype</term><term>Prédisposition génétique à une maladie</term><term>Récepteur ErbB-2 (antagonistes et inhibiteurs)</term><term>Récepteur ErbB-2 (génétique)</term><term>Récepteur ErbB-2 (métabolisme)</term><term>Sélection de patients</term><term>Trastuzumab</term><term>Tumeurs du sein (anatomopathologie)</term><term>Tumeurs du sein (enzymologie)</term><term>Tumeurs du sein (génétique)</term><term>Tumeurs du sein (traitement médicamenteux)</term><term>Valeur prédictive des tests</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Receptor, ErbB-2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Receptor, ErbB-2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Receptor, ErbB-2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term><term>Antineoplastic Agents</term><term>Protein Kinase Inhibitors</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Tumeurs du sein</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Récepteur ErbB-2</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Tumeurs du sein</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Récepteur ErbB-2</term><term>Tumeurs du sein</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Récepteur ErbB-2</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Tumeurs du sein</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Anticorps monoclonaux humanisés</term><term>Antinéoplasiques</term><term>Inhibiteurs de protéines kinases</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Centromere</term><term>Chromosomes, Human, Pair 17</term><term>Female</term><term>Gene Amplification</term><term>Gene Dosage</term><term>Genetic Heterogeneity</term><term>Genetic Predisposition to Disease</term><term>Humans</term><term>In Situ Hybridization</term><term>Patient Selection</term><term>Phenotype</term><term>Precision Medicine</term><term>Predictive Value of Tests</term><term>Trastuzumab</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Amplification de gène</term><term>Centromère</term><term>Chromosomes humains de la paire 17</term><term>Dosage génique</term><term>Femelle</term><term>Humains</term><term>Hybridation in situ</term><term>Hétérogénéité génétique</term><term>Médecine individualisée</term><term>Phénotype</term><term>Prédisposition génétique à une maladie</term><term>Sélection de patients</term><term>Trastuzumab</term><term>Valeur prédictive des tests</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Trastuzumab-containing therapy is a standard of care for patients with HER2+ breast cancer. HER2 status is routinely assigned using in situ hybridization to assess HER2 gene amplification, but interpretation of in situ hybridization results may be challenging in tumors with chromosome 17 polysomy or intratumoral genetic heterogeneity. Apparent chromosome 17 polysomy, defined by increased chromosome enumeration probe 17 (CEP17) signal number, is a common genetic aberration in breast cancer and represents an alternative mechanism for increasing HER2 copy number. Some studies have linked elevated CEP17 count ('polysomy') with adverse clinicopathologic features and HER2 overexpression, although there are numerous discrepancies in the literature. There is evidence that elevated CEP17 ('polysomy') count might account for trastuzumab response in tumors with normal HER2:CEP17 ratios. Nonetheless, recent studies establish that apparent 'polysomy' (CEP17 increase) is usually related to focal pericentromeric gains rather than true polysomy. Assigning HER2 status may also be complex where multiple cell subclones with distinct HER2 amplification characteristics coexist within the same tumor. Such genetic heterogeneity affects up to 40% of breast cancers when assessed according to a College of American Pathologists guideline, although other definitions have been proposed. Recent data have associated heterogeneity with unfavorable clinicopathologic variables and poor prognosis. Genetically heterogeneous tumors harboring HER2-amplified subclones have the potential to benefit from trastuzumab, but this has yet to be evaluated in clinical studies. In this review, we discuss the implications of apparent polysomy 17 and genetic heterogeneity for assigning HER2 status in clinical practice. Among our recommendations, we support the use of mean HER2 copy number rather than HER2:CEP17 ratio to define HER2 positivity in cases where coamplification of the centromere might mask HER2 amplification. We also highlight a need to harmonize in situ hybridization scoring methodology to support accurate HER2 status determination, particularly where there is evidence of heterogeneity.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Brésil</li><li>Canada</li><li>France</li><li>Italie</li><li>Japon</li><li>Pays-Bas</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Auvergne (région administrative)</li><li>Auvergne-Rhône-Alpes</li><li>District de Kassel</li><li>Grand Londres</li><li>Hesse (Land)</li><li>Hollande-Septentrionale</li><li>Lombardie</li><li>Ontario</li><li>Région de Kantō</li><li>État de São Paulo</li></region><settlement><li>Amsterdam</li><li>Cassel (Hesse)</li><li>Clermont-Ferrand</li><li>Londres</li><li>Milan</li><li>São Paulo</li><li>Tokyo</li><li>Toronto</li></settlement><orgName><li>Université d'Amsterdam</li><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><region name="Ontario"><name sortKey="Hanna, Wedad M" sort="Hanna, Wedad M" uniqKey="Hanna W" first="Wedad M" last="Hanna">Wedad M. Hanna</name></region></country><country name="Allemagne"><region name="Hesse (Land)"><name sortKey="Ruschoff, Josef" sort="Ruschoff, Josef" uniqKey="Ruschoff J" first="Josef" last="Rüschoff">Josef Rüschoff</name></region></country><country name="Australie"><noRegion><name sortKey="Bilous, Michael" sort="Bilous, Michael" uniqKey="Bilous M" first="Michael" last="Bilous">Michael Bilous</name></noRegion></country><country name="Brésil"><region name="État de São Paulo"><name sortKey="Coudry, Renata A" sort="Coudry, Renata A" uniqKey="Coudry R" first="Renata A" last="Coudry">Renata A. Coudry</name></region></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Dowsett, Mitch" sort="Dowsett, Mitch" uniqKey="Dowsett M" first="Mitch" last="Dowsett">Mitch Dowsett</name></region></country><country name="Japon"><region name="Région de Kantō"><name sortKey="Osamura, Robert Y" sort="Osamura, Robert Y" uniqKey="Osamura R" first="Robert Y" last="Osamura">Robert Y. Osamura</name></region></country><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Penault Llorca, Frederique" sort="Penault Llorca, Frederique" uniqKey="Penault Llorca F" first="Frédérique" last="Penault-Llorca">Frédérique Penault-Llorca</name></region></country><country name="Pays-Bas"><region name="Hollande-Septentrionale"><name sortKey="Van De Vijver, Marc" sort="Van De Vijver, Marc" uniqKey="Van De Vijver M" first="Marc" last="Van De Vijver">Marc Van De Vijver</name></region></country><country name="Italie"><region name="Lombardie"><name sortKey="Viale, Giuseppe" sort="Viale, Giuseppe" uniqKey="Viale G" first="Giuseppe" last="Viale">Giuseppe Viale</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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