Details

Autor(en) / Beteiligte

• 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

Titel

HER-2 amplification is highly homogenous in gastric cancer

Ist Teil von

• Human pathology, 2009-06, Vol.40 (6), p.769-777

Ort / Verlag

New York, NY: Elsevier Inc

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.