Intratumoral heterogeneity determines discordant results of diagnostic tests for human epidermal growth factor receptor (HER) 2 in gastric cancer specimens |
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Authors: | Yang Jiyuan Luo Hesheng Li Yan Li Junchuan Cai Zhiqiang Su Xiaoyan Dai Danqing Du Wei Chen Tingxuan Chen Ming |
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Institution: | (1) Department of Digestion, Renmin Hospital of WuHan University, Zhiyang Street 99, HuBei, WuHan, 430060, China;(2) Department of Laboratory Medicine, Renmin Hospital of WuHan University, Zhiyang Street 99, HuBei, WuHan, 430060, China;(3) Department of Oncology, First Affiliated Hospital of Yangtze University, JingZhou, HuBei, China |
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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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