title: HER-2 amplification is highly homogenous in gastric cancer.
abstract: Her-2 is the molecular target for antibody-based treatment of breast cancer (trastuzumab). The potential benefit of anti-Her-2 therapy is currently investigated in several other HER-2-amplified cancers including gastric cancer. Although HER-2 amplification occurs in more than 10% of gastric cancers, potential heterogeneity of HER-2 amplification and overexpression could represent a major drawback for anti-Her-2 therapy. To address the potential applicability of trastuzumab in gastric cancer, tissue microarray sections of 166 gastric adenocarcinomas and 69 lymph node metastases were analyzed for Her-2 overexpression and amplification using Food and Drug Administration-approved reagents for immunohistochemistry and fluorescence in situ hybridization. HER-2 amplification was seen in 27 (16%) of 166 gastric adenocarcinomas. Amplification was typically high level with more than 20 HER-2 copies per tumor cell and a HER-2/centromere 17 ratio >3. Amplification was associated with intestinal tumor phenotype but unrelated to survival, grading, pT, pN, or pM. Identical HER-2 status was found in primary tumor and their matched lymph node metastases. Moreover, HER-2 and Topoisomerase IIalpha coamplification analysis of 3 to 16 large sections from 8 Her-2-positive gastric cancers did not reveal any heterogeneity of the amplicon site. The high level of HER-2 amplification in combination with the homogeneity of its expression in primary and metastatic tumors argues for a possible therapeutic utility of trastuzumab in HER-2-amplified gastric adenocarcinomas.
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany. a.marx@uke.de
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Marx
authors.forename: Lars
authors.initials: L
authors.lastname: Tharun
authors.forename: Johanna
authors.initials: J
authors.lastname: Muth
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Dancau
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Emre
authors.initials: E
authors.lastname: Yekebas
authors.forename: Jussuf T
authors.initials: JT
authors.lastname: Kaifi
authors.forename: Martina
authors.initials: M
authors.lastname: Mirlacher
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D046888:Tissue Array Analysis; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human