HER2 testing in gastric cancer diagnosis: insights on variables influencing HER2-positivity from a large, multicenter, observational study in Germany

Baretton, Gustavo; Kreipe, Hans; Schirmacher, Peter; Gaiser, Timo; Hofheinz, Ralf; Berghäuser, K. H.; Koch, Winfried; Künzel, C; Morris, Stefanie; Rüschoff, Josef

doi:10.1007/s00428-019-02541-9

Cited by 20 publications

(27 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…with clinicopathological characteristics of the 80 patients are shown in Table 3. Among the various detection methods, tissue HER2 positive status showed correlation with Lauren classification, especially intestinal type, rather than diffuse type (64.2% vs. 21.7%; P = 0.021), as previously reported 14,15 . The determination of the HER2 status by tissue ddPCR showed significant correlation with aggressive behaviors, including advanced gastric cancer (P = 0.022), presence of lymphatic invasion (P = 0.003), and presence of lymph node metastasis (P = 0.036).…”

Section: Correlation Between Clinicopathological Factors and Her2 Stasupporting

confidence: 81%

Comparative analysis of HER2 copy number between plasma and tissue samples in gastric cancer using droplet digital PCR

Kim

Nam

Seo

et al. 2020

Sci Rep

View full text Add to dashboard Cite

In this study, we measured the human epidermal growth factor receptor 2 (HER2) copy number in both tissue and plasma samples of gastric cancer patients by using droplet digital polymerase chain reaction (ddPCR) method. Eighty gastric cancer patients were enrolled and both formalin-fixed and paraffinembedded tissue and preoperative plasma samples were collected. HER2 status was determined by HER2 immunohistochemistry (IHC)/silver in situ hybridization (SISH) in tissue samples and ddPCR of the target gene HER2 and the reference gene eukaryotic translation initiation factor 2C, 1 in both tissue and plasma. The concordance rate of tissue HER2 status determined by IHC/SISH and HER2 ddpcR was 90.0% (72/80), and the sensitivity and specificity of tissue ddPCR were 85.0% and 95.0%, respectively. The concordance rate of plasma ddPCR and IHC/SISH was 63.8% (51/80). The sensitivity, specificity, positive predictive value, and negative predictive value of plasma HER2 ddPCR were 37.5%, 90.0%, 79.0%, and 59.0%, respectively. As HER2 measurement by tissue ddpcR showed a high concordance rate with HER2 status by IHC/SISH, it could replace tissue IHC/SISH testing in gastric cancer. These findings may contribute to the development of tissue and plasma HER2 testing that would be useful in daily practice.

show abstract

Section: Correlation Between Clinicopathological Factors and Her2 Stasupporting

confidence: 81%

Comparative analysis of HER2 copy number between plasma and tissue samples in gastric cancer using droplet digital PCR

Kim

Nam

Seo

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The present study revealed HER2 positivity in 11.5% of patients, as well as an association between positive HER2 status and the intestinal type, according to Lauren classification and lack of mucinous component of the tumor. These findings are consistent with those from a previous study (20), and other studies have also indicated a relationship between HER2 positivity and tumor location in the gastrointestinal junction (8,21). The HER2 oncogene is located on the long arm of the chromosome 17, near the centromere (22), as shown in Fig.…”

Section: Discussionsupporting

confidence: 93%

“…The accurate evaluation of HER2 status is essential for the appropriate use of anti-HER2 therapy (8,9). To assess HER2 positivity, protein expression is evaluated by immunohistochemistry (IHC) and if the result is equivocal (2+), fluorescence in situ hybridization (FISH) is performed to assess HER2 gene amplification (4)(5)(6).…”

Section: Impact Of Chromosome 17 Centromere Copy Number Increase On Pmentioning

confidence: 99%

Impact of chromosome 17 centromere copy number increase on patient survival and human epidermal growth factor receptor 2 expression in gastric adenocarcinoma

Ciesielski¹,

Szajewski²,

Walczak³

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

The accurate evaluation of human epidermal growth factor receptor 2 (HER2) status is essential for the appropriate use of targeted therapies. An increased number of chromosome 17 centromere enumeration probe (CEP17) signals may underrate fluorescence in situ hybridization (FISH) outcomes, resulting in false-negative or a false-equivocal HER2 status assessment. The aim of the present study was to assess the frequency of CEP17 copy number increase (CNI), its effects on HER2 protein expression (and the subsequent effects on tumor cells), and the survival outcomes of patients with gastric cancer. Archival primary tumor samples from 244 patients that underwent gastric resection for adenocarcinoma were retrieved for both HER2 protein expression analysis (using immunochemistry) and HER2 gene amplification (using FISH). The associations between HER2 status, CEP17 CNI and multiple clinicopathological parameters (including survival outcome), were assessed. The relationship between CEP17 CNI and HER2 protein upregulation was also investigated. CEP17 CNI was detected in 17.2% of cases, and a strong association between CEP17 CNI and HER2 upregulation was revealed. The impact of CEP17 CNI on survival did not reach statistical significance. Consequently, CEP17 CNI was discovered to be strongly associated with HER2 upregulation in tumor cells, which may characterize a critical issue in HER2 testing. Therefore, the eligibility for HER2-targeted agents in CEP17 CNI-positive patients warrants further recognition.

show abstract

“…Esophagogastric junction cancers (EGJC) are more likely to be HER2-positive (HER21) than distal GCs. [2][3][4][5][6] Trastuzumab, a humanized HER2-targeting immunoglobulin G1 monoclonal antibody in combination with chemotherapy, was approved for first-line treatment of HER21 metastatic (m)GC based on the randomized controlled Trastuzumab for Gastric Cancer (ToGA) study. 7 However, the improvement in median overall survival (OS) in the subgroup, which was used to license treatment with trastuzumab, of 4.2 months compared with chemotherapy alone was moderate and duration of response is limited in the majority of patients.…”

Section: Introductionmentioning

confidence: 99%

HER2 Expression, Test Deviations, and Their Impact on Survival in Metastatic Gastric Cancer: Results From the Prospective Multicenter VARIANZ Study

Haffner

Schierle

Raimúndez

et al. 2021

JCO

View full text Add to dashboard Cite

PURPOSE Trastuzumab is the only approved targeted drug for first-line treatment of human epidermal growth factor receptor 2–positive (HER2+) metastatic gastric cancer (mGC). However, not all patients respond and most eventually progress. The multicenter VARIANZ study aimed to investigate the background of response and resistance to trastuzumab in mGC. METHODS Patients receiving medical treatment for mGC were prospectively recruited in 35 German sites and followed for up to 48 months. HER2 status was assessed centrally by immunohistochemistry and chromogenic in situ hybridization. In addition, HER2 gene expression was assessed using qPCR. RESULTS Five hundred forty-eight patients were enrolled, and 77 had HER2+ mGC by central assessment (14.1%). A high deviation rate of 22.7% between central and local test results was seen. Patients who received trastuzumab for centrally confirmed HER2+ mGC (central HER2+/local HER2+) lived significantly longer as compared with patients who received trastuzumab for local HER2+ but central HER2− mGC (20.5 months, n = 60 v 10.9 months, n = 65; hazard ratio, 0.42; 95% CI, 8.2 to 14.4; P < .001). In the centrally confirmed cohort, significantly more tumor cells stained HER2+ than in the unconfirmed cohort, and the HER2 amplification ratio was significantly higher. A minimum of 40% HER2+ tumor cells and a HER2 amplification ratio of ≥ 3.0 were calculated as optimized thresholds for predicting benefit from trastuzumab. CONCLUSION Significant discrepancies in HER2 assessment of mGC were found in tumor specimens with intermediate HER2 expression. Borderline HER2 positivity and heterogeneity of HER2 expression should be considered as resistance factors for HER2-targeting treatment of mGC. HER2 thresholds should be reconsidered. Detailed reports with quantification of HER2 expression and amplification levels may improve selection of patients for HER2-directed treatment.

show abstract

HER2 testing in gastric cancer diagnosis: insights on variables influencing HER2-positivity from a large, multicenter, observational study in Germany

Cited by 20 publications

References 26 publications

Comparative analysis of HER2 copy number between plasma and tissue samples in gastric cancer using droplet digital PCR

Comparative analysis of HER2 copy number between plasma and tissue samples in gastric cancer using droplet digital PCR

Impact of chromosome 17 centromere copy number increase on patient survival and human epidermal growth factor receptor 2 expression in gastric adenocarcinoma

HER2 Expression, Test Deviations, and Their Impact on Survival in Metastatic Gastric Cancer: Results From the Prospective Multicenter VARIANZ Study

Contact Info

Product

Resources

About