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Published on: December 5, 2017
HER-2 amplification is highly homogenous in gastric cancer
Andreas H Marx1, Lars Tharun, Johanna Muth
1Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany. a.marx@uke.de
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.
Insights
Trastuzumab shows potential for HER-2 amplified gastric cancers. HER-2 amplification is common and consistent in primary and metastatic tumors, supporting its therapeutic use.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Human Epidermal growth factor Receptor 2 (HER-2) is a target for antibody therapy in breast cancer.
- HER-2 amplification occurs in over 10% of gastric cancers, but heterogeneity may limit treatment efficacy.
Purpose of the Study:
- To evaluate the applicability of trastuzumab in gastric cancer by assessing HER-2 amplification and overexpression.
- To investigate potential heterogeneity of HER-2 amplification in gastric adenocarcinomas and lymph node metastases.
Main Methods:
- Tissue microarray sections from 166 gastric adenocarcinomas and 69 lymph node metastases were analyzed.
- Immunohistochemistry and fluorescence in situ hybridization (FISH) were used with FDA-approved reagents.
- HER-2 and Topoisomerase IIalpha coamplification was analyzed in large tissue sections from 8 HER-2-positive gastric cancers.
Main Results:
- HER-2 amplification was detected in 16% (27/166) of gastric adenocarcinomas, typically at high levels.
- Amplification was associated with intestinal phenotype but not survival or other clinical parameters.
- Identical HER-2 status was observed in primary tumors and matched lymph node metastases, with no heterogeneity found in amplicon sites.
Conclusions:
- The high-level, homogeneous HER-2 amplification in primary and metastatic gastric tumors supports the potential therapeutic utility of trastuzumab.
- Gastric adenocarcinomas with HER-2 amplification are candidates for anti-HER-2 therapy.
