title: Intratumoral heterogeneity determines discordant results of diagnostic tests for human epidermal growth factor receptor (HER) 2 in gastric cancer specimens.
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.
authors.affiliation: Department of Digestion, Renmin Hospital of WuHan University, HuBei, WuHan, China.
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Yang
authors.forename: Hesheng
authors.initials: H
authors.lastname: Luo
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Junchuan
authors.initials: J
authors.lastname: Li
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Cai
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Su
authors.forename: Danqing
authors.initials: D
authors.lastname: Dai
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.forename: Tingxuan
authors.initials: T
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human