Determination of Her-2/Neu Status in Breast Carcinoma: Comparative Analysis of Immunohistochemistry and Fluorescent In Situ Hybridization View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2000-01

AUTHORS

Rafael E Jimenez, Tracy Wallis, Pam Tabasczka, Daniel W Visscher

ABSTRACT

Her-2/neu (H2N) status in breast carcinoma has been considered a prognostic factor that may have therapeutic implications; however, the correlation between H2N overexpression and gene amplification has not been completely defined. A consecutive series of ductal carcinomas (34 invasive and 7 in situ) were analyzed by fluorescent in situ hybridization for H2N gene and chromosome 17 copy number using touch preps of intact cells and by immunohistochemistry, using three different commercial antibodies to H2N protein (Zymed, clone 31G7; Ventana, clone CB11; and Dako, polyclonal) in corresponding formalin-fixed, paraffin-embedded tissue sections. Gene amplification was classified as unequivocal if more than five signals were present in more than 80% of the counted nuclei and absent if more than 80% of the nuclei counted contained two or fewer gene copies. Cases that did not fulfill the above criteria were considered equivocal for amplification. Immunostaining was classified as follows: 0 = no staining; 1+ = faint, incomplete membranous pattern; 2+ = moderate, complete membranous pattern; 3+ = strong membranous pattern. Of the 34 invasive tumors, 10 (29%) had unequivocal gene amplification. Furthermore, all had more than 10 copies of the gene in more than 60% of the counted nuclei. An additional nine cases (26%) had equivocal amplification, which was usually the result of chromosome 17 aneuploidy (seven of nine) or heterogeneity. With the Zymed and Dako antibodies, all tumors with 3+ staining had unequivocal gene amplification and all cases with 2+, 1+, or 0 staining were negative or equivocal for gene amplification. With the Ventana antibody, all cases with 3+ staining had unequivocal gene amplification, but two cases with unequivocal amplification by fluorescent in situ hybridization exhibited 1+ staining. Moderate (2+) H2N staining was observed in one case, three cases, and five cases with the Ventana, Dako, and Zymed reagents, respectively, and did not correlate with H2N gene copy number. Discordance between H2N and chromosome 17 copy number was not a useful means of defining amplification. Two cases of ductal carcinoma in situ with the Zymed antibody and two with the Dako antibody showed 3+ staining despite lack of unequivocal gene amplification. We conclude that (1) strong H2N immunostaining is highly associated with gene amplification, although there is minor variation in sensitivity between different antibodies; (2) a subset of breast carcinomas (3 to 15%) demonstrate moderate H2N staining without evidence of amplification, and it is unclear whether they represent highly sensitive staining or are a subset of cases that show overexpression without amplification; (3) gene amplification, as detected by fluorescent in situ hybridization, is associated with at least 10 gene copies per nucleus, and lower gene copy duplication (3 to 4/nucleus) is frequent, usually the result of chromosome 17 polysomy, and not associated with high-level overexpression; (5) overexpression of H2N without amplification may be more frequent in ductal carcinoma in situ, implying a different role in the biology of preinvasive versus invasive neoplasm. More... »

PAGES

3880007

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/modpathol.3880007

DOI

http://dx.doi.org/10.1038/modpathol.3880007

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1011441671

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10658908


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Oncology and Carcinogenesis", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Breast Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Carcinoma, Ductal, Breast", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Carcinoma, Intraductal, Noninfiltrating", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Count", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Chromosomes, Human, Pair 17", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Female", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Gene Amplification", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Genes, erbB-2", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Immunohistochemistry", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "In Situ Hybridization, Fluorescence", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Prospective Studies", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Receptor, ErbB-2", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Wayne State University", 
          "id": "https://www.grid.ac/institutes/grid.254444.7", 
          "name": [
            "Department of Pathology, Harper Hospital, the Karmanos Cancer Institute and Wayne State University, Detroit, Michigan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Jimenez", 
        "givenName": "Rafael E", 
        "id": "sg:person.01313033035.62", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01313033035.62"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Wayne State University", 
          "id": "https://www.grid.ac/institutes/grid.254444.7", 
          "name": [
            "Department of Pathology, Harper Hospital, the Karmanos Cancer Institute and Wayne State University, Detroit, Michigan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wallis", 
        "givenName": "Tracy", 
        "id": "sg:person.013507427034.65", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013507427034.65"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Wayne State University", 
          "id": "https://www.grid.ac/institutes/grid.254444.7", 
          "name": [
            "Department of Pathology, Harper Hospital, the Karmanos Cancer Institute and Wayne State University, Detroit, Michigan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Tabasczka", 
        "givenName": "Pam", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Wayne State University", 
          "id": "https://www.grid.ac/institutes/grid.254444.7", 
          "name": [
            "Department of Pathology, Harper Hospital, the Karmanos Cancer Institute and Wayne State University, Detroit, Michigan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Visscher", 
        "givenName": "Daniel W", 
        "id": "sg:person.07611541437.04", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07611541437.04"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1002/cyto.990210117", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006247844"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cyto.990210117", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006247844"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1159/000333683", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012353648"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cyto.990210109", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012731458"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cyto.990210109", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012731458"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/bjc.1995.146", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016467825", 
          "https://doi.org/10.1038/bjc.1995.146"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/bjc.1995.146", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016467825", 
          "https://doi.org/10.1038/bjc.1995.146"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/(sici)1097-0142(19970601)79:11<2162::aid-cncr14>3.0.co;2-u", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020241505"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/bf00192631", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029887849", 
          "https://doi.org/10.1007/bf00192631"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0046-8177(92)90257-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036231539"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/1097-0142(19920815)70:4<770::aid-cncr2820700409>3.0.co;2-u", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036734223"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0046-8177(97)90157-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043877463"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/bf01806187", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043909841", 
          "https://doi.org/10.1007/bf01806187"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/bf01806187", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043909841", 
          "https://doi.org/10.1007/bf01806187"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/ijc.2910490504", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049237181"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.2470152", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1062539373"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.1992.10.7.1044", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1075798136"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1082424677", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1082561095", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/j.1460-2075.1993.tb05891.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1082650792"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.1996.14.3.737", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1082882775"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1082915087", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083122347", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.1997.15.8.2894", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1083129505"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083134147", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083141937", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083200463", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083227937", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083234821", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083290314", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2000-01", 
    "datePublishedReg": "2000-01-01", 
    "description": "Her-2/neu (H2N) status in breast carcinoma has been considered a prognostic factor that may have therapeutic implications; however, the correlation between H2N overexpression and gene amplification has not been completely defined. A consecutive series of ductal carcinomas (34 invasive and 7 in situ) were analyzed by fluorescent in situ hybridization for H2N gene and chromosome 17 copy number using touch preps of intact cells and by immunohistochemistry, using three different commercial antibodies to H2N protein (Zymed, clone 31G7; Ventana, clone CB11; and Dako, polyclonal) in corresponding formalin-fixed, paraffin-embedded tissue sections. Gene amplification was classified as unequivocal if more than five signals were present in more than 80% of the counted nuclei and absent if more than 80% of the nuclei counted contained two or fewer gene copies. Cases that did not fulfill the above criteria were considered equivocal for amplification. Immunostaining was classified as follows: 0 = no staining; 1+ = faint, incomplete membranous pattern; 2+ = moderate, complete membranous pattern; 3+ = strong membranous pattern. Of the 34 invasive tumors, 10 (29%) had unequivocal gene amplification. Furthermore, all had more than 10 copies of the gene in more than 60% of the counted nuclei. An additional nine cases (26%) had equivocal amplification, which was usually the result of chromosome 17 aneuploidy (seven of nine) or heterogeneity. With the Zymed and Dako antibodies, all tumors with 3+ staining had unequivocal gene amplification and all cases with 2+, 1+, or 0 staining were negative or equivocal for gene amplification. With the Ventana antibody, all cases with 3+ staining had unequivocal gene amplification, but two cases with unequivocal amplification by fluorescent in situ hybridization exhibited 1+ staining. Moderate (2+) H2N staining was observed in one case, three cases, and five cases with the Ventana, Dako, and Zymed reagents, respectively, and did not correlate with H2N gene copy number. Discordance between H2N and chromosome 17 copy number was not a useful means of defining amplification. Two cases of ductal carcinoma in situ with the Zymed antibody and two with the Dako antibody showed 3+ staining despite lack of unequivocal gene amplification. We conclude that (1) strong H2N immunostaining is highly associated with gene amplification, although there is minor variation in sensitivity between different antibodies; (2) a subset of breast carcinomas (3 to 15%) demonstrate moderate H2N staining without evidence of amplification, and it is unclear whether they represent highly sensitive staining or are a subset of cases that show overexpression without amplification; (3) gene amplification, as detected by fluorescent in situ hybridization, is associated with at least 10 gene copies per nucleus, and lower gene copy duplication (3 to 4/nucleus) is frequent, usually the result of chromosome 17 polysomy, and not associated with high-level overexpression; (5) overexpression of H2N without amplification may be more frequent in ductal carcinoma in situ, implying a different role in the biology of preinvasive versus invasive neoplasm.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/modpathol.3880007", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1098208", 
        "issn": [
          "0893-3952", 
          "1530-0285"
        ], 
        "name": "Modern Pathology", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "13"
      }
    ], 
    "name": "Determination of Her-2/Neu Status in Breast Carcinoma: Comparative Analysis of Immunohistochemistry and Fluorescent In Situ Hybridization", 
    "pagination": "3880007", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "36833d79e2b820f26c668d90564ac0619527d699686a87d90ccd187c1aca472a"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "10658908"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "8806605"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/modpathol.3880007"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1011441671"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/modpathol.3880007", 
      "https://app.dimensions.ai/details/publication/pub.1011441671"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T12:25", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000362_0000000362/records_87104_00000000.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "http://www.nature.com/articles/3880007"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/modpathol.3880007'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/modpathol.3880007'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/modpathol.3880007'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/modpathol.3880007'


 

This table displays all metadata directly associated to this object as RDF triples.

212 TRIPLES      21 PREDICATES      68 URIs      34 LITERALS      22 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/modpathol.3880007 schema:about N22ec7df5c51c4b6d8d4d877fb3443f10
2 N26d096a0b79f438386d34d3bc37ac19c
3 N446ef1a403004682820729f6a2c6f6dd
4 N546bfe7c9fbc4c3a8ca399f7c3bedd81
5 N76cc4baae77c4f52ba4b45c5ca819709
6 N8633984874ed4fda99dbb53c0e9b0055
7 N8b8117b7bd834bf18587a9a66e6a3d3f
8 N988d9acc7c20428f97737febaa1a64bc
9 N989bd4faac764b3ba4d6e38f48e828a6
10 Nc332777af2b84b0abaaf3c049b24d3fd
11 Nd32ed2b6d89c4f4eba9d2af6a24f1e65
12 Nda6caa1b034448cd9cb65b542be6000b
13 Ne5fd89563b284f4894fd657474238d01
14 anzsrc-for:11
15 anzsrc-for:1112
16 schema:author N86d79ba3a1f647aab052a28b412491be
17 schema:citation sg:pub.10.1007/bf00192631
18 sg:pub.10.1007/bf01806187
19 sg:pub.10.1038/bjc.1995.146
20 https://app.dimensions.ai/details/publication/pub.1082424677
21 https://app.dimensions.ai/details/publication/pub.1082561095
22 https://app.dimensions.ai/details/publication/pub.1082915087
23 https://app.dimensions.ai/details/publication/pub.1083122347
24 https://app.dimensions.ai/details/publication/pub.1083134147
25 https://app.dimensions.ai/details/publication/pub.1083141937
26 https://app.dimensions.ai/details/publication/pub.1083200463
27 https://app.dimensions.ai/details/publication/pub.1083227937
28 https://app.dimensions.ai/details/publication/pub.1083234821
29 https://app.dimensions.ai/details/publication/pub.1083290314
30 https://doi.org/10.1002/(sici)1097-0142(19970601)79:11<2162::aid-cncr14>3.0.co;2-u
31 https://doi.org/10.1002/1097-0142(19920815)70:4<770::aid-cncr2820700409>3.0.co;2-u
32 https://doi.org/10.1002/cyto.990210109
33 https://doi.org/10.1002/cyto.990210117
34 https://doi.org/10.1002/ijc.2910490504
35 https://doi.org/10.1002/j.1460-2075.1993.tb05891.x
36 https://doi.org/10.1016/0046-8177(92)90257-4
37 https://doi.org/10.1016/s0046-8177(97)90157-x
38 https://doi.org/10.1126/science.2470152
39 https://doi.org/10.1159/000333683
40 https://doi.org/10.1200/jco.1992.10.7.1044
41 https://doi.org/10.1200/jco.1996.14.3.737
42 https://doi.org/10.1200/jco.1997.15.8.2894
43 schema:datePublished 2000-01
44 schema:datePublishedReg 2000-01-01
45 schema:description Her-2/neu (H2N) status in breast carcinoma has been considered a prognostic factor that may have therapeutic implications; however, the correlation between H2N overexpression and gene amplification has not been completely defined. A consecutive series of ductal carcinomas (34 invasive and 7 in situ) were analyzed by fluorescent in situ hybridization for H2N gene and chromosome 17 copy number using touch preps of intact cells and by immunohistochemistry, using three different commercial antibodies to H2N protein (Zymed, clone 31G7; Ventana, clone CB11; and Dako, polyclonal) in corresponding formalin-fixed, paraffin-embedded tissue sections. Gene amplification was classified as unequivocal if more than five signals were present in more than 80% of the counted nuclei and absent if more than 80% of the nuclei counted contained two or fewer gene copies. Cases that did not fulfill the above criteria were considered equivocal for amplification. Immunostaining was classified as follows: 0 = no staining; 1+ = faint, incomplete membranous pattern; 2+ = moderate, complete membranous pattern; 3+ = strong membranous pattern. Of the 34 invasive tumors, 10 (29%) had unequivocal gene amplification. Furthermore, all had more than 10 copies of the gene in more than 60% of the counted nuclei. An additional nine cases (26%) had equivocal amplification, which was usually the result of chromosome 17 aneuploidy (seven of nine) or heterogeneity. With the Zymed and Dako antibodies, all tumors with 3+ staining had unequivocal gene amplification and all cases with 2+, 1+, or 0 staining were negative or equivocal for gene amplification. With the Ventana antibody, all cases with 3+ staining had unequivocal gene amplification, but two cases with unequivocal amplification by fluorescent in situ hybridization exhibited 1+ staining. Moderate (2+) H2N staining was observed in one case, three cases, and five cases with the Ventana, Dako, and Zymed reagents, respectively, and did not correlate with H2N gene copy number. Discordance between H2N and chromosome 17 copy number was not a useful means of defining amplification. Two cases of ductal carcinoma in situ with the Zymed antibody and two with the Dako antibody showed 3+ staining despite lack of unequivocal gene amplification. We conclude that (1) strong H2N immunostaining is highly associated with gene amplification, although there is minor variation in sensitivity between different antibodies; (2) a subset of breast carcinomas (3 to 15%) demonstrate moderate H2N staining without evidence of amplification, and it is unclear whether they represent highly sensitive staining or are a subset of cases that show overexpression without amplification; (3) gene amplification, as detected by fluorescent in situ hybridization, is associated with at least 10 gene copies per nucleus, and lower gene copy duplication (3 to 4/nucleus) is frequent, usually the result of chromosome 17 polysomy, and not associated with high-level overexpression; (5) overexpression of H2N without amplification may be more frequent in ductal carcinoma in situ, implying a different role in the biology of preinvasive versus invasive neoplasm.
46 schema:genre research_article
47 schema:inLanguage en
48 schema:isAccessibleForFree true
49 schema:isPartOf Ncbdd9922ecac4dde9725130b91835d74
50 Ne3a9832f075441c4b107a5e9f317f2a6
51 sg:journal.1098208
52 schema:name Determination of Her-2/Neu Status in Breast Carcinoma: Comparative Analysis of Immunohistochemistry and Fluorescent In Situ Hybridization
53 schema:pagination 3880007
54 schema:productId N6be0f2c804d948eea91df3e4d8f4541e
55 N78a5106f23bb42499b219f7cf834e22a
56 N812f1d0d9cb84f5ba41a70f8181ea3f6
57 Nc55f5c8835b1471988f9a6df1d844314
58 Nd2616193c1ee4c9f9343560b78648063
59 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011441671
60 https://doi.org/10.1038/modpathol.3880007
61 schema:sdDatePublished 2019-04-11T12:25
62 schema:sdLicense https://scigraph.springernature.com/explorer/license/
63 schema:sdPublisher Nb11be1e483954fbcaf065a141596d6f3
64 schema:url http://www.nature.com/articles/3880007
65 sgo:license sg:explorer/license/
66 sgo:sdDataset articles
67 rdf:type schema:ScholarlyArticle
68 N11ea5c258a5b4bffaabda5ffb774ea8e rdf:first N62b94daa42294888abfa992b4883bce1
69 rdf:rest Nc22866f523a3463dae9e2debb0882502
70 N22ec7df5c51c4b6d8d4d877fb3443f10 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
71 schema:name Receptor, ErbB-2
72 rdf:type schema:DefinedTerm
73 N26d096a0b79f438386d34d3bc37ac19c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
74 schema:name Cell Count
75 rdf:type schema:DefinedTerm
76 N446ef1a403004682820729f6a2c6f6dd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
77 schema:name Breast Neoplasms
78 rdf:type schema:DefinedTerm
79 N546bfe7c9fbc4c3a8ca399f7c3bedd81 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
80 schema:name Chromosomes, Human, Pair 17
81 rdf:type schema:DefinedTerm
82 N62b94daa42294888abfa992b4883bce1 schema:affiliation https://www.grid.ac/institutes/grid.254444.7
83 schema:familyName Tabasczka
84 schema:givenName Pam
85 rdf:type schema:Person
86 N6be0f2c804d948eea91df3e4d8f4541e schema:name nlm_unique_id
87 schema:value 8806605
88 rdf:type schema:PropertyValue
89 N76cc4baae77c4f52ba4b45c5ca819709 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
90 schema:name Carcinoma, Intraductal, Noninfiltrating
91 rdf:type schema:DefinedTerm
92 N78a5106f23bb42499b219f7cf834e22a schema:name readcube_id
93 schema:value 36833d79e2b820f26c668d90564ac0619527d699686a87d90ccd187c1aca472a
94 rdf:type schema:PropertyValue
95 N812f1d0d9cb84f5ba41a70f8181ea3f6 schema:name doi
96 schema:value 10.1038/modpathol.3880007
97 rdf:type schema:PropertyValue
98 N8633984874ed4fda99dbb53c0e9b0055 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
99 schema:name Prospective Studies
100 rdf:type schema:DefinedTerm
101 N86d79ba3a1f647aab052a28b412491be rdf:first sg:person.01313033035.62
102 rdf:rest Nd90da926bda141f7a0d901f42815929b
103 N8b8117b7bd834bf18587a9a66e6a3d3f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
104 schema:name In Situ Hybridization, Fluorescence
105 rdf:type schema:DefinedTerm
106 N988d9acc7c20428f97737febaa1a64bc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
107 schema:name Carcinoma, Ductal, Breast
108 rdf:type schema:DefinedTerm
109 N989bd4faac764b3ba4d6e38f48e828a6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
110 schema:name Humans
111 rdf:type schema:DefinedTerm
112 Nb11be1e483954fbcaf065a141596d6f3 schema:name Springer Nature - SN SciGraph project
113 rdf:type schema:Organization
114 Nc22866f523a3463dae9e2debb0882502 rdf:first sg:person.07611541437.04
115 rdf:rest rdf:nil
116 Nc332777af2b84b0abaaf3c049b24d3fd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
117 schema:name Female
118 rdf:type schema:DefinedTerm
119 Nc55f5c8835b1471988f9a6df1d844314 schema:name dimensions_id
120 schema:value pub.1011441671
121 rdf:type schema:PropertyValue
122 Ncbdd9922ecac4dde9725130b91835d74 schema:volumeNumber 13
123 rdf:type schema:PublicationVolume
124 Nd2616193c1ee4c9f9343560b78648063 schema:name pubmed_id
125 schema:value 10658908
126 rdf:type schema:PropertyValue
127 Nd32ed2b6d89c4f4eba9d2af6a24f1e65 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
128 schema:name Immunohistochemistry
129 rdf:type schema:DefinedTerm
130 Nd90da926bda141f7a0d901f42815929b rdf:first sg:person.013507427034.65
131 rdf:rest N11ea5c258a5b4bffaabda5ffb774ea8e
132 Nda6caa1b034448cd9cb65b542be6000b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
133 schema:name Genes, erbB-2
134 rdf:type schema:DefinedTerm
135 Ne3a9832f075441c4b107a5e9f317f2a6 schema:issueNumber 1
136 rdf:type schema:PublicationIssue
137 Ne5fd89563b284f4894fd657474238d01 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
138 schema:name Gene Amplification
139 rdf:type schema:DefinedTerm
140 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
141 schema:name Medical and Health Sciences
142 rdf:type schema:DefinedTerm
143 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
144 schema:name Oncology and Carcinogenesis
145 rdf:type schema:DefinedTerm
146 sg:journal.1098208 schema:issn 0893-3952
147 1530-0285
148 schema:name Modern Pathology
149 rdf:type schema:Periodical
150 sg:person.01313033035.62 schema:affiliation https://www.grid.ac/institutes/grid.254444.7
151 schema:familyName Jimenez
152 schema:givenName Rafael E
153 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01313033035.62
154 rdf:type schema:Person
155 sg:person.013507427034.65 schema:affiliation https://www.grid.ac/institutes/grid.254444.7
156 schema:familyName Wallis
157 schema:givenName Tracy
158 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013507427034.65
159 rdf:type schema:Person
160 sg:person.07611541437.04 schema:affiliation https://www.grid.ac/institutes/grid.254444.7
161 schema:familyName Visscher
162 schema:givenName Daniel W
163 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07611541437.04
164 rdf:type schema:Person
165 sg:pub.10.1007/bf00192631 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029887849
166 https://doi.org/10.1007/bf00192631
167 rdf:type schema:CreativeWork
168 sg:pub.10.1007/bf01806187 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043909841
169 https://doi.org/10.1007/bf01806187
170 rdf:type schema:CreativeWork
171 sg:pub.10.1038/bjc.1995.146 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016467825
172 https://doi.org/10.1038/bjc.1995.146
173 rdf:type schema:CreativeWork
174 https://app.dimensions.ai/details/publication/pub.1082424677 schema:CreativeWork
175 https://app.dimensions.ai/details/publication/pub.1082561095 schema:CreativeWork
176 https://app.dimensions.ai/details/publication/pub.1082915087 schema:CreativeWork
177 https://app.dimensions.ai/details/publication/pub.1083122347 schema:CreativeWork
178 https://app.dimensions.ai/details/publication/pub.1083134147 schema:CreativeWork
179 https://app.dimensions.ai/details/publication/pub.1083141937 schema:CreativeWork
180 https://app.dimensions.ai/details/publication/pub.1083200463 schema:CreativeWork
181 https://app.dimensions.ai/details/publication/pub.1083227937 schema:CreativeWork
182 https://app.dimensions.ai/details/publication/pub.1083234821 schema:CreativeWork
183 https://app.dimensions.ai/details/publication/pub.1083290314 schema:CreativeWork
184 https://doi.org/10.1002/(sici)1097-0142(19970601)79:11<2162::aid-cncr14>3.0.co;2-u schema:sameAs https://app.dimensions.ai/details/publication/pub.1020241505
185 rdf:type schema:CreativeWork
186 https://doi.org/10.1002/1097-0142(19920815)70:4<770::aid-cncr2820700409>3.0.co;2-u schema:sameAs https://app.dimensions.ai/details/publication/pub.1036734223
187 rdf:type schema:CreativeWork
188 https://doi.org/10.1002/cyto.990210109 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012731458
189 rdf:type schema:CreativeWork
190 https://doi.org/10.1002/cyto.990210117 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006247844
191 rdf:type schema:CreativeWork
192 https://doi.org/10.1002/ijc.2910490504 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049237181
193 rdf:type schema:CreativeWork
194 https://doi.org/10.1002/j.1460-2075.1993.tb05891.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1082650792
195 rdf:type schema:CreativeWork
196 https://doi.org/10.1016/0046-8177(92)90257-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036231539
197 rdf:type schema:CreativeWork
198 https://doi.org/10.1016/s0046-8177(97)90157-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1043877463
199 rdf:type schema:CreativeWork
200 https://doi.org/10.1126/science.2470152 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062539373
201 rdf:type schema:CreativeWork
202 https://doi.org/10.1159/000333683 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012353648
203 rdf:type schema:CreativeWork
204 https://doi.org/10.1200/jco.1992.10.7.1044 schema:sameAs https://app.dimensions.ai/details/publication/pub.1075798136
205 rdf:type schema:CreativeWork
206 https://doi.org/10.1200/jco.1996.14.3.737 schema:sameAs https://app.dimensions.ai/details/publication/pub.1082882775
207 rdf:type schema:CreativeWork
208 https://doi.org/10.1200/jco.1997.15.8.2894 schema:sameAs https://app.dimensions.ai/details/publication/pub.1083129505
209 rdf:type schema:CreativeWork
210 https://www.grid.ac/institutes/grid.254444.7 schema:alternateName Wayne State University
211 schema:name Department of Pathology, Harper Hospital, the Karmanos Cancer Institute and Wayne State University, Detroit, Michigan
212 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...