HER2 gene assessment in liquid biopsy of gastric and esophagogastric junction cancer patients qualified for surgery

Grzegorz Wallner,Anna Grenda,Jadwiga Sierocińska-Sawa,Tomasz Skoczylas,Kamila Wojas-Krawczyk,Paweł Krawczyk,Janusz Milanowski

doi:10.1186/s12876-020-01531-5

Abstract

BackgroundAmplification 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.MethodsWe 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).ResultsWe 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).ConclusionsWe 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.

Highlights

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)
The median number of HER2 gene copies measured by Quantitative polymerase chain reaction (qPCR) was 1.85 ± 1.54. 40 (51%) patients had more than 1.85 HER2 gene copy number and 38 (49%) patients had less than 1.85 HER2 gene copy number
The analysis showed that the HER2 gene copy number in liquid biopsy was higher in GC and EGJC patients compared to healthy people (p = 0.01, Fig. 1a)

Summary

Introduction

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. 20% of Caucasian patients with metastatic gastric cancer are HER2-positive. Despite the methods used for assessment of HER2 status, tests results may be non-diagnostic, due to the nature of the cancer tissue and the difficulties in its proper preparation. There is possibility to use liquid biopsy as a non-invasive method to assess HER2 amplification in serum or plasma samples [9, 10]. We attempted to assess the copy number variation (CNV) of the HER2 gene in circulating free DNA (circulating tumor DNA, ct-DNA) in patients with gastric or esophagogastric junction cancers qualified for surgery

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Discussion

Conclusion