Comparison of HER2 Status Before and After Trastuzumab-based Chemotherapy in Patients With Advanced Gastric Cancer

Kijima, Takashi; Arigami, Takaaki; Uenosono, Yoshikazu; Hiraki, Takao; Yanagita, Shigehiro; Matsushita, Daisuke; Okubo, Kan; Shimonosono, Masataka; Ishigami, Sumiya; Maemura, Kosei; Tanimoto, Akihide; Natsugoe, Shoji

doi:10.21873/anticanres.13927

Cited by 22 publications

(13 citation statements)

References 27 publications

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“…At present, the probes for the detection of HER2 gene status are mostly double probes containing the HER2 gene and the centromeric region of chromosome 17 (CEP17), where the gene is located. It was found that HER2 protein was expressed in breast cancer, ovarian cancer, gastric cancer, and other cancers [ 5 – 7 ]. The inducing factors of gastric cancer are mainly related to the activation of carcinogenic factors and the deactivation of tumor suppressor factors.…”

Section: Introductionmentioning

confidence: 99%

Significance of Detection of the HER2 Gene and PD-1/PD-L1 in Gastric Cancer

Yun

Wang

Jiang

et al. 2020

Journal of Oncology

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Objective. To explore the relationship between the HER2 gene and PD-1/PD-L1 in gastric cancer and its significance. Methods. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were used to detect HER2 protein expression, HER2 gene amplification, and PD-1/PD-L1 expression in 78 cases of gastric cancer. Results. The expression rate of HER2 protein was 43.6% (34/78), of which 19.4% (14/78) were HER2 3+, 14.1% (11/78) were HER2 2+, and 11.5% (9/78) were HER2 1+. The results showed that 19.2% (15/78) of samples had HER2 gene amplification, 3.8% (3/78) of samples had a HER2/CEP17 ratio <2.0, and 19.2% (15/78) of samples had HER2 gene amplificationf and HER2 copy/cell ≥6.0, as detected by FISH. The positive rate of PD-L1 was 38.5% (30/78) in gastric cancer cells and 50.0% (39/78) in interstitial lymphocytes. The expression of the HER2 gene, PD-L1, and PD-1 in gastric cancer was correlated with the stage and lymph node metastasis of gastric cancer ( P < 0.05 ). Conclusions. The combined detection of the HER2 gene and PD-1/PD-L1 in gastric cancer provides an important reference index for the prognosis of gastric cancer and the benefit of targeted antitumor drugs.

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Section: Introductionmentioning

confidence: 99%

Significance of Detection of the HER2 Gene and PD-1/PD-L1 in Gastric Cancer

Yun

Wang

Jiang

et al. 2020

Journal of Oncology

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“…Despite improvements in the diagnosis and treatment of patients with GC, the 5-year survival rate is still poor, only 30%–35% [ 9 , 10 ]. With many GCs diagnosed every year, the need for standardized prognostic and predictive markers is emphasized in many studies published on this subject; nonetheless, much remains unknown [ 14 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…The main reason of the difficulty in assessing HER2 in GCs is the intratumorally heterogeneity of its expression, which occurs in 69%–75% of cases [ 4 – 7 , 9 , 18 , 19 ]. In this paper, we emphasize and confirm this heterogeneity, which is present in the same tumor, between primary tumor and metastatic tissue and even in the same tumor gland.…”

Section: Discussionmentioning

confidence: 99%

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HER2 Heterogeneity in Gastric Cancer: A Comparative Study, Using Two Commercial Antibodies

Satala

Jung

Staden

et al. 2020

Journal of Oncology

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Background. Although amplification of the gene encoding human epidermal growth factor receptor 2 (HER2) is used as an indicator for response to trastuzumab, the reported response rate is low, and few patients with gastric cancer (GC) benefit from this individualized therapy. The aim of this study was to examine the expression of c-erbB-2 oncoprotein (HER2), in GC samples, using two commercial immunohistochemical (IHC) antibodies, and to validate the results by checking HER2 gene amplification by fluorescence in situ hybridization (FISH). Methods. We assessed the IHC expression of HER2 using the polyclonal antibody from Dako and CB11 clone from Leica, in 93 consecutive cases of GC samples. In all of the cases, FISH analysis was also performed using the BOND-MAX platform. Results. No significant difference was observed between the two HER2 antibodies. Of the 93 cases, 22.58% demonstrated at least focal and 1+ HER2 positivity. Seven cases (7.53%) exhibited 3+ expression, and another 7 carcinomas (7.53%) were equivocal (2+). HER2 amplification was seen in 11 cases (11.83%), 10 of which were differentiated adenocarcinomas. In 5 of the cases, 2–5 sections were examined, which proved the extremely high intratumorally/intraglandular heterogeneity. FISH heterogeneity was higher in cases with only 2+ positivity on IHC assessment, compared with those showing at least one small focus of 3+ overexpression. HER2 amplification proved to be an independent negative prognostic factor. Conclusions. Due to the highly heterogeneous aspect of GC, at least 3-4 slides should be assessed by IHC, before considering a tumor to be HER2-negative. In cases with small 3+ foci representing less than 5% of tumor and in equivocal (2+) cases, FISH analysis remains the gold standard method.

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“…Trastuzumab in association with systemic cytotoxic chemotherapy is a therapeutic option for patients with advanced or metastatic HER-2 positive gastric carcinoma. The status of the HER-2 overexpression or gene ampli cation is an important predictive marker in gastric cancer [16,17]. The aim of this study was to investigate the EBV infection by in situ hybridization (ISH), and mismatch repair (MMR) status and PD-L1 expression using immunohistochemistry (IHC) in surgically treated GC patients.…”

Section: Introductionmentioning

confidence: 99%

Clinic-pathological Features of Epstein-barr Virus Infection, Microsatellite Instability, Tumor Mutation Burden and PD-L1 Status in 2504 Chinese Gastric Cancer Patients

Zhang

2020

Preprint

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Objectives: Gastric cancer is the 4th most common cancer worldwide. Different subtype showed unique molecular features that could potentially guide therapeutic decisions. The aim of this study was to investigate the Epstein-Barr virus infection, microsatellite instability status, PD-L1 expression and gene mutation in surgically treated gastric cancer patients. Methods: We reviewed all GC patients who underwent potentially curative gastroectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 and 2018 from a prospective collected medical database. We analyzed the clinic-pathological factors associated with immunohistochemistry profiles. We also analyzed gene changes through next-generation sequencing. Results: d-MMR gastric cancer patients are more likely to expression programmed death-ligand 1 (p<0.001, programmed death-ligand 1 cut off value 1%). EBV-positive and d-MMR patients were identified in 4% and 7.5% of the 2504 gastric cancer patients, respectively. The MLH1/PMS2 negative case number was 126. The MSH2/MSH6 negative case number was 14. d-MMR status was related to diffuse/mixed group (p<0.05), but not related to tumor differentiation. In our study, the microsatellite instability results detected by next generation sequencing and d-MMR gastric cancer results detected by immunohistochemistry were in high consistency. d-MMR gastric cancer patients had more microsatellite instability core. Many pathogenic genes were detected in microsatellite instability gastric cancer patients, such as POLE, ETV6, TP53, BRCA, RNF43 and other genes. Conclusion: Through immunohistochemistry and next generation sequencing, we got MSI status, protein expression, TMB and gene changes of GC, which provided a theoretical basis for future G clinical treatment.

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Comparison of HER2 Status Before and After Trastuzumab-based Chemotherapy in Patients With Advanced Gastric Cancer

Cited by 22 publications

References 27 publications

Significance of Detection of the HER2 Gene and PD-1/PD-L1 in Gastric Cancer

Significance of Detection of the HER2 Gene and PD-1/PD-L1 in Gastric Cancer

HER2 Heterogeneity in Gastric Cancer: A Comparative Study, Using Two Commercial Antibodies

Clinic-pathological Features of Epstein-barr Virus Infection, Microsatellite Instability, Tumor Mutation Burden and PD-L1 Status in 2504 Chinese Gastric Cancer Patients

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