Hybridization for human epidermal growth factor receptor 2 testing in gastric carcinoma: a comparison of fluorescence in-situ hybridization with a novel fully automated dual-colour silver in-situ hybridization method

García-García, Elena; Gómez‐Martín, Carlos; Angulo, Bárbara; Conde, Esther; Suárez-Gauthier, Ana; Adrados, Magdalena; Perna, Cristian; Rodríguez‐Peralto, José Luis; Hidalgo, Manuel; López‐Ríos, Fernando

doi:10.1111/j.1365-2559.2011.03894.x

Cited by 42 publications

(28 citation statements)

References 43 publications

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“…Eighteen patients (14%) were detected to have a positive HER2 status both in the biopsy and the resection material (concordance: 96.1%) (23). In our study, we found a higher rate of HER2 discordance in the primary GC and the paired metastasis compared with the rates reported in previous studies.…”

Section: Discussioncontrasting

confidence: 52%

Discordances in HER2 status between primary gastric cancer and corresponding metastatic sites

Gümüşay

Benekli

Ekinci

et al. 2015

Japanese Journal of Clinical Oncology

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Objective: Determination of human epidermal growth factor receptor-2 status in advanced gastric cancer is important in clinical decision making. In the trastuzumab for GC trial, trastuzumab-based therapy demonstrated a significant overall survival benefit in patients with human epidermal growth factor receptor-2-positive advanced gastric cancer. Human epidermal growth factor receptor-2 discordance in gastric cancer primary and its metastases has been long debated. The aim of the study was to evaluate the rate of human epidermal growth factor receptor-2 discordance and its effect on treatment decisions in advanced gastric cancer. Methods: A total of 74 patients with advanced gastric cancer were included in the study. Both immunohistochemical staining and dual-color silver in situ hybridization were performed in all patients to evaluate the human epidermal growth factor receptor-2 status of the primary lesion and paired metastasis. Results: The assessment of human epidermal growth factor receptor-2 status with the immunohistochemical staining method and dual-color silver in situ hybridization revealed a discordance rate of 9.5 and 16.2%, respectively. However, this discordance was clinically meaningful in only one patient leading to a change in treatment decision. While this patient had a human epidermal growth factor receptor-2-negative status in primary tumor (immunohistochemical = 0, dual-color silver in situ hybridization = negative), the human epidermal growth factor receptor-2 status was positive for liver metastasis (immunohistochemical = 2+, dual-color silver in situ hybridization = positive). Trastuzumab was added to the chemotherapy regimen. Conclusions: In this study, we found a higher rate of human epidermal growth factor receptor-2 discordance between primary gastric tumor and metastatic lesions compared with the rates reported in previous studies. Detection of a human epidermal growth factor receptor-2-positive metastasis with a human epidermal growth factor receptor-2-negative primary tumor suggests that investigation of human epidermal growth factor receptor-2 is also required for the metastatic lesion and that trastuzumab could be administered in the case of a positive result.

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Section: Discussioncontrasting

confidence: 52%

Discordances in HER2 status between primary gastric cancer and corresponding metastatic sites

Gümüşay

Benekli

Ekinci

et al. 2015

Japanese Journal of Clinical Oncology

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“…Our results are similar to the few studies published to date comparing these methods in gastric and GEJ tumors. [2][3][4] In accordance with our study, concordance rates of 96% and 100% were observed in 2 studies. 2,4 Langer et al 4 observed lower concordance, but this study was limited by the use of tissue microarrays including tissue cores from different tumor areas.…”

Section: Discussionsupporting

confidence: 95%

HER2 In Situ Hybridization in Gastric and Gastroesophageal Adenocarcinoma

Grin

Bauer²,

Streutker³

2013

Applied Immunohistochemistry &Amp; Molecular Morphology

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Patients with gastric and gastroesophageal junction (GEJ) adenocarcinomas that are HER2 positive by immunohistochemistry (IHC) or in situ hybridization show a significant survival benefit with trastuzumab therapy. In situ hybridization is traditionally done by fluorescence in situ hybridization (FISH), despite some limitations. An alternative is the dual in situ hybridization (Dual ISH) technique that is fully automated and uses differentially labeled CEP17 and HER2 probes that can be read by light microscopy on 1 slide. The aim of this study was to assess the utility of Dual ISH in gastric/GEJ cancer and to compare the results with those obtained by IHC and FISH. Cases of gastric/GEJ adenocarcinoma were analyzed by IHC, FISH, and Dual ISH and the correlation between methods calculated. Results for 50 patients were available. There was a 98% (49/50) concordance rate between Dual ISH and FISH. One discrepant case was nonamplified by FISH but showed focal amplification by Dual ISH. Discrepancy was attributed to tumor heterogeneity, which was a frequent finding (78% of HER2-positive cases). There was excellent correlation between Dual ISH and FISH for assessment of HER2 amplification. Dual ISH was rapid, easy to interpret, and maintained cell morphology, which was valuable in identifying tumor heterogeneity.

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“…42,105 Many methods for detecting HER2 CNVs, including flourescence in situ hybridization, in situ hybridization, chromogenic in situ hybridization and silver in situ hybridization, have been demonstrated as effective approaches. 42,101,106 Moreover, the HER2:chr17 (chromosome 17) ratio may be an additional index to eliminate incorrect HER2 status determination in GC. 107 The utilization of molecularly targeted therapeutics against HER2 has emerged as a significant strategy for advanced GCs.…”

Section: Chromosomementioning

confidence: 99%

Gastric cancer and gene copy number variation: emerging cancer drivers for targeted therapy

2015

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Gastric cancer (GC) is among the most common malignancy in the world with poor prognosis and limited treatment options. It has been established that gastric carcinogenesis is caused by a complex interaction between host and environmental factors. Copy number variation (CNV) refers to a form of genomic structural variation that results in abnormal gene copy numbers, including gene amplification, gain, loss and deletion. DNA CNV is an important influential factor for the expression of both protein-coding and non-coding genes, affecting the activity of various signaling pathways. CNV arises as a result of preferential selection that favors cancer development, and thus, targeting the amplified 'driver genes' in GC may provide novel opportunities for personalized therapy. The detection of CNVs in chromosomal or mitochondrial DNA from tissue or blood samples may assist the diagnosis, prognosis and targeted therapy of GC. In this review, we discuss the recent CNV discoveries that shed light on the molecular pathogenesis of GC, with a specific emphasis on CNVs that display diagnostic, prognostic or therapeutic significances in GC.

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Hybridization for human epidermal growth factor receptor 2 testing in gastric carcinoma: a comparison of fluorescence in-situ hybridization with a novel fully automated dual-colour silver in-situ hybridization method

Cited by 42 publications

References 43 publications

Discordances in HER2 status between primary gastric cancer and corresponding metastatic sites

Discordances in HER2 status between primary gastric cancer and corresponding metastatic sites

HER2 In Situ Hybridization in Gastric and Gastroesophageal Adenocarcinoma

Gastric cancer and gene copy number variation: emerging cancer drivers for targeted therapy

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