Chair and Department of Pneumology, Oncology and Allergology, Medical University of Lublin, Jaczewskiego 8, 20-090, Lublin, Poland.
II Chair and Department of General and Gastrointestinal Surgery and Surgical Oncology of the Alimentary Tract, Medical University of Lublin, Staszica 16, 20-080, Lublin, Poland.
BMC Gastroenterol. 2020 Nov 16;20(1):382. doi: 10.1186/s12876-020-01531-5.
Amplification of HER2 gene (ERBB2) and overexpression of HER2 protein on cancer cells are found in 10-26% of gastric cancer (GC) and esophagogastric junction cancer (EGJC). Gene copy number variation (CNV) could be detected in these patients in liquid biopsy and in cancer cells.
We analysed HER2 gene CNV used qPCR method in 87 sera collected from GC and EGJC patients before surgical treatment and in 40 sera obtained from healthy donors. HER2 gene CNV was also assessed in formalin-fixed paraffin-embedded (FFPE) tumor tissue. Furthermore, we assessed the number of HER2 gene copies and HER2 expression in cancer cells using the fluorescent in situ hybridization method (FISH) and immunohistochemistry (IHC).
We found that the HER2 gene copy number in liquid biopsy was higher in GC and EGJC patients compared to healthy people (p = 0.01). Moreover, EGJC patients had higher number of HER2 gene copies than healthy donors (p = 0.0016). HER2 CNV examination could distinguish healthy individuals and patients with gastric or esophagogastric junction cancers with sensitivity and specificity of 58% and 98% (AUC = 0.707, 95% CI 0.593-0.821, p = 0.004). We found that patients with a high copy number of the HER2 gene in the tumor tissue assessed by qPCR (but not by FISH) have significantly more often a high number of HER2 gene copies in liquid biopsy (p = 0.04).
We suggested that HER2 testing in liquid biopsy could be used as an auxiliary method to analysis of HER2 status in tumor tissue in gastric or esophagogastric junction cancers.
HER2 基因（ERBB2）扩增和 HER2 蛋白在癌细胞中的过表达在 10-26%的胃癌（GC）和食管胃交界癌（EGJC）中被发现。在这些患者的液体活检和癌细胞中可以检测到基因拷贝数变异（CNV）。
我们使用 qPCR 方法分析了 87 例 GC 和 EGJC 患者手术前采集的血清和 40 例健康供者血清中的 HER2 基因 CNV。还评估了福尔马林固定石蜡包埋（FFPE）肿瘤组织中的 HER2 基因 CNV。此外，我们使用荧光原位杂交（FISH）和免疫组织化学（IHC）方法评估了癌细胞中 HER2 基因拷贝数和 HER2 表达。
我们发现液体活检中 GC 和 EGJC 患者的 HER2 基因拷贝数高于健康人（p=0.01）。此外，EGJC 患者的 HER2 基因拷贝数高于健康供者（p=0.0016）。HER2 CNV 检查可以区分健康个体和胃或食管胃交界癌患者，其敏感性和特异性分别为 58%和 98%（AUC=0.707，95%CI 0.593-0.821，p=0.004）。我们发现，通过 qPCR 评估的肿瘤组织中 HER2 基因高拷贝数的患者，其液体活检中 HER2 基因拷贝数也显著较高（p=0.04）。
我们提出，液体活检中的 HER2 检测可作为分析胃或食管胃交界癌肿瘤组织中 HER2 状态的辅助方法。
