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Intratumoral Heterogeneity Determines Discordant Results of Diagnostic Tests for Human Epidermal Growth Factor Receptor (HER) 2 in Gastric Cancer Specimens

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Abstract

Accurate assessment of human epidermal growth factor receptor (HER) 2 is essential for efficient selection of patients who may benefit from therapies targeting this surface receptor (e.g., trastuzumab). Intratumoral heterogeneity of HER2 expression may potentially contribute to inaccurate assessment of HER2 status. To clarify intratumoral heterogeneity of HER2 expression and its potential clinical impact on assessment of HER2 status, we analyzed 148 endoscopic biopsy specimens and 117 excisional tumor specimens collected from 148 patients with primary gastric cancer. Specifically, we assessed HER2 protein overexpression and gene amplification using, respectively, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). There were 28 IHC-positive cases and 25 FISH-positive cases among these 148 patients. Heterogeneous HER2 protein expression was demonstrated in 23 of 29 (79.3%) IHC-positive cases, while gene expression heterogeneity was found in 11 of 25 (44.0%) FISH-positive cases. Intratumoral heterogeneity was the main reason of discordant results between IHC and FISH or between endoscopic biopsy and excisional tumor specimens. The clinical significance and impact of intratumoral HER2 expression heterogeneity on treatment outcome in gastric cancer require further studies.

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Authors and Affiliations

  1. Department of Digestion, Renmin Hospital of WuHan University, Zhiyang Street 99, HuBei, WuHan, 430060, China

    Jiyuan Yang & Hesheng Luo

  2. Department of Laboratory Medicine, Renmin Hospital of WuHan University, Zhiyang Street 99, HuBei, WuHan, 430060, China

    Yan Li & Ming Chen

  3. Department of Oncology, First Affiliated Hospital of Yangtze University, JingZhou, HuBei, China

    Jiyuan Yang, Junchuan Li, Zhiqiang Cai, Xiaoyan Su, Danqing Dai, Wei Du, Tingxuan Chen & Ming Chen

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Correspondence to Hesheng Luo or Ming Chen.

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Yang, J., Luo, H., Li, Y. et al. Intratumoral Heterogeneity Determines Discordant Results of Diagnostic Tests for Human Epidermal Growth Factor Receptor (HER) 2 in Gastric Cancer Specimens. Cell Biochem Biophys 62, 221–228 (2012). https://doi.org/10.1007/s12013-011-9286-1

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  • DOI: https://doi.org/10.1007/s12013-011-9286-1

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