HER2 Status and Its Heterogeneity in Gastric Carcinoma of Vietnamese Patient

Abstract

BackgroundHuman epidermal growth factor receptor 2 (HER2) is related to the pathogenesis and poor outcome of numerous types of carcinomas, including gastric carcinoma. Gastric cancer patients with HER2 positivity have become potential candidates for targeted therapy with trastuzumab.MethodsWe investigated 208 gastric cancer specimens using immunohistochemistry (IHC), fluorescence in situ hybridization and dual in situ hybridization (ISH). We also investigated the concordance between IHC and ISH. The correlation between HER2 status and various clinicopathological findings was also investigated. ResultsIn total, 15.9% (33/208) and 24.5% (51/208) of gastric cancers showed HER2 gene amplification and protein overexpression, respectively. A high level of concordance between ISH and IHC analyses (91.3%, κ = 0.76) was found. A significant correlation between HER2 status and intestinal-type (p < .05) and differentiated carcinomas (p < .05) was also noted. The HER2 heterogeneity was high in gastric cancers; we found 68.8% phenotypic heterogeneity and 57.6% genotypic heterogeneity. Heterogeneity in HER2 protein expression and gene amplification showed a close association with diffuse histologic type and IHC 2+. ConclusionsHER2 protein overexpression and gene amplification were detected in 24.5% and 15.9% of gastric cancer specimens, respectively. Intestinal-type showed a higher level of HER2 protein overexpression and gene amplification than diffuse type. HER2 status also showed a significant relationship with well- and moderately-differentiated carcinomas. The ratio of phenotypic and genotypic heterogeneity of HER2 was high in gastric carcinomas and was associated with HER2 IHC 2+ and diffuse histologic type.

Blockade of ITGA2 Induces Apoptosis and Inhibits Cell Migration in Gastric Cancer

“…Some of the antibodies such as trastuzumab (an anti-human epidermal growth factor receptor 2 (HER2) antibody) and bevacizumab (an anti-vascular endothelial growth factor (VEGF) antibody) have been used for advanced gastric cancer [ 7 – 9 ]. However, these therapeutic antibodies do not treat all gastric cancer patients since less than 20% of gastric cancers showed HER2 gene amplification and approximately 25% of gastric cancers showed HER2 protein overexpression [ 10 ]. Furthermore, multiple clinical trials on the efficacies of trastuzumab and bevacizumab indicate that these antibodies may not improve the patient survival over chemotherapy alone [ 11 – 13 ].…”

Identifying HER2 from serum‐derived exosomes in advanced gastric cancer as a promising biomarker for assessing tissue HER2 status and predicting the efficacy of trastuzumab‐based therapy

“…2,38 Anh Thu Phan et al reported a high level of concordance between ISH and IHC analyses, an amplification rate of the HER2 gene of 15.9% and protein overexpression of the HER2 gene of 24.5%, and elevated HER2 heterogeneity in gastric cancers (68.8% phenotypic heterogeneity and 57.6% genotypic heterogeneity). 38 HER2 positivity (overexpression [IHC3+] and/or gene amplification [FISH positive]) has been reported in 22% of advanced G/GEJ cancers but varies by tumor location and type in ToGA study, where HER2 staining (≤30% stained cells) by IHC was observed in almost 50% of cases. 14 Intratumoral phenotypic heterogeneity was also frequently observed with a high incidence of 63.5% in IHC 2+ cases and 28.3% in IHC 3+ cases, and phenotypic heterogeneity was more frequently observed than genotypic heterogeneity (48.8% vs. 26.8%).…”

“…Moreover, variations in different study population ethnicity, cancer histotype, HER2 status evaluation assay utilization and tumor heterogeneity might produce divergent outcomes in sundry studies 2,38 . Anh Thu Phan et al reported a high level of concordance between ISH and IHC analyses, an amplification rate of the HER2 gene of 15.9% and protein overexpression of the HER2 gene of 24.5%, and elevated HER2 heterogeneity in gastric cancers (68.8% phenotypic heterogeneity and 57.6% genotypic heterogeneity) 38 . HER2 positivity (overexpression [IHC3+] and/or gene amplification [FISH positive]) has been reported in 22% of advanced G/GEJ cancers but varies by tumor location and type in ToGA study, where HER2 staining (≤30% stained cells) by IHC was observed in almost 50% of cases 14 .…”

The Expression of E-cadherin & HER2 in Gastric Carcinoma

“…Her2 expression was detected in 6.6 percent of male patients and 10% of female patients in the current study but had no statistical significance. Phan et al [31] discovered that 26.6 percent of male and 20.3 percent of female patients have HER2. Roy et al [29] confirmed that Her2 was positive in 66% of males and 36% of females with no statistical significance.…”