HER2 gene assessment in liquid biopsy of gastric and esophagogastric junction cancer patients qualified for surgery
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RESEARCH ARTICLE
Open Access
HER2 gene assessment in liquid biopsy of gastric and esophagogastric junction cancer patients qualified for surgery Anna Grenda1* , Kamila Wojas‑Krawczyk1, Tomasz Skoczylas2, Paweł Krawczyk1, Jadwiga Sierocińska‑Sawa3, Grzegorz Wallner2 and Janusz Milanowski1
Abstract Background: 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. Methods: 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 expres‑ sion in cancer cells using the fluorescent in situ hybridization method (FISH) and immunohistochemistry (IHC). Results: 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 esophagogas‑ tric 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). Conclusions: 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. Keywords: Gastric cancer, Esophagogastric cancer, HER2 copy number, Liquid biopsy Background Amplification of HER2 gene (ERBB2) and overexpression of HER2 protein on cancer cells is found in 10–26% of gastric cancer (GC) and esophagogastric junction cancer (EGJC) [1–3]. Approximately 20% of Caucasian patients with metastatic gastric cancer are HER2-positive. Unlike breast cancer, HER2 positivity is not an independent prognostic factor of patients’ outcome in metastatic *Correspondence: [email protected] 1 Chair and Department of Pneumology, Oncology and Allergology, Medical University of Lublin, Jaczewskiego 8, 20‑090 Lublin, Poland Full list of author information is available at the end of the article
gastric or EGJC cancers [4]. However, there is evidence that trastuzumab, as neoadjuvant, adjuvant treatment, in combination with oxaliplatin and capecitabine in patients with HER2 overexpressing gastric adenocarcinoma, led to recurrence-free survival of at least 18 months after surgery. Trastuzumab can also be used in combination with oxaliplatin and fluorouracil in the first-line treatment of patients with advanced gastric cancer with high HER2 expressi
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