HER-2 amplification is highly homogenous in gastric cancer

被引：220

作者：

Marx, Andreas H. ^{[1
]}

Tharun, Lars ^{[1
]}

Muth, Johanna ^{[1
]}

Dancau, Ana-Maria ^{[2
]}

Simon, Ronald ^{[1
]}

Yekebas, Emre ^{[2
]}

Kaifi, Jussuf T. ^{[2
]}

Mirlacher, Martina ^{[1
]}

Bruemmendorf, Tim H. ^{[3
]}

Bokemeyer, Carsten ^{[3
]}

Izbicki, Jakob R. ^{[2
]}

Sauter, Guide ^{[1
]}

机构：

[1] Univ Med Ctr Hamburg Eppendorf, Inst Pathol, D-20246 Hamburg, Germany

[2] Univ Med Ctr Hamburg Eppendorf, Dept Surg, D-20246 Hamburg, Germany

[3] Univ Med Ctr Hamburg Eppendorf, Ctr Canc, D-20246 Hamburg, Germany

来源：

HUMAN PATHOLOGY | 2009年 / 40卷 / 06期

关键词：

Her-2; Gastric cancer; Trastuzumab; Immunohistochemistry; TMA; FISH; IN-SITU HYBRIDIZATION; METASTATIC BREAST-CANCER; ALPHA GENE AMPLIFICATION; TISSUE MICROARRAYS; ERBB RECEPTORS; TRASTUZUMAB; IMMUNOHISTOCHEMISTRY; OVEREXPRESSION; CARCINOMA; EXPRESSION;

D O I：

10.1016/j.humpath.2008.11.014

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

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 turner phenotype but unrelated to survival, grading, pT, pN, or pM. Identical HER-2 status was found in primary tumor and their snatched lymph node metastases. Moreover, HER-2 and Topoisomerase II alpha coamplification analysis of 3 to 16 large sections Prom 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 turners argues for a possible therapeutic utility of trastuzumab in HER-2-amplified gastric adenocarcinomas. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：769 / 777

页数：9

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