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

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 expression 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 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). 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.

Circulating Tumor DNA in Gastric Adenocarcinoma: Future Clinical Applications and Perspectives

“…Of interest, it has been shown that cfDNA levels in GC are more elevated than those in benign and pre-cancerous conditions, such as gastric adenomas. Based on this, a study incorporating cfDNA is underway in South Korea (NCT04665687) to identify biomarkers discriminating between neoplastic and non-neoplastic gastric lesions [30][31][32][33].…”

Targeted and Immunotherapy Approaches in HER2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma: A New Era

“…Expanding HER2 -positivity detection methods to include liquid biopsies and next-generation sequencing could potentially provide reliable noninvasive alternatives beyond the traditional IHC and FISH testing approaches. [ 54 , 55 ] With the explosion of immunotherapy research within the last decade, one of the most exciting strategies in the future to combat HER2 + gastric or GEJ cancer is the combinatorial approach of various HER2 -targeting agents with checkpoint inhibitors, CAR-T cells, and vaccines. Through simultaneous blockade of different pathways and taking advantage of the immune system, there continues to be progress and hope in the field of advanced HER2 -positive gastric or GEJ adenocarcinoma.…”

The Role of ctDNA in Gastric Cancer

“…However, amplifications in HER2 are only present in a subset of patients with GC (approximately 20%). Amongst several other similar studies, Grenda et al detected the HER2 gene copy number at higher concentrations in the blood samples of patients with GC compared to healthy controls, with a sensitivity of 58% and a specificity of 98% ( p = 0.004) [ 45 ].…”