HER-2 amplification is highly homogenous in gastric cancer

Summary 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...

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Bibliographic Details
Published in:Human pathology 2009-06, Vol.40 (6), p.769-777
Main Authors: Marx, Andreas H., MD, Tharun, Lars, Muth, Johanna, Dancau, Ana-Maria, MD, Simon, Ronald, PhD, Yekebas, Emre, MD, Kaifi, Jussuf T., MD, Mirlacher, Martina, Brümmendorf, Tim H., MD, Bokemeyer, Carsten, MD, Izbicki, Jakob R., MD, Sauter, Guido, MD
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal - therapeutic use
Antibodies, Monoclonal, Humanized
Antigens, Neoplasm - genetics
Antineoplastic agents
Biological and medical sciences
Breast cancer
Cancer therapies
Chemotherapy
DNA Topoisomerases, Type II - genetics
DNA-Binding Proteins - genetics
FDA approval
Female
FISH
Gastric cancer
Gastroenterology. Liver. Pancreas. Abdomen
Gene Amplification
Genes, erbB-2 - genetics
Her-2
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Lymphatic Metastasis
Male
Medical sciences
Middle Aged
Pathology
Pharmacology. Drug treatments
Receptor, ErbB-2 - immunology
Stomach Neoplasms - drug therapy
Stomach Neoplasms - genetics
Stomach Neoplasms - pathology
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tissue Array Analysis
TMA
Trastuzumab
Tumors
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Summary:Summary 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 IIα 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.
ISSN:0046-8177
1532-8392
DOI:10.1016/j.humpath.2008.11.014