scholarly journals Comparison of fluorescence in-situ hybridisation with dual-colour in-situ hybridisation for assessment of HER2 gene amplification of breast cancer in Hong Kong

2016 ◽  
Author(s):  
Scott MC Tang ◽  
◽  
Inda S Soong ◽  
MY Luk ◽  
Dacita TK Suen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hong Kong ◽  
Gene Amplification ◽  
In Situ Hybridisation ◽  
Fluorescence In Situ Hybridisation ◽  
Her2 Gene ◽  
Her2 Gene Amplification ◽  
Dual Colour

scholarly journals HER2 gene amplification in patients with breast cancer with equivocal IHC results

2011 ◽  
Vol 64 (12) ◽  
pp. 1069-1072 ◽  
Author(s):  
Sybren L Meijer ◽  
Jelle Wesseling ◽  
Vincent T Smit ◽  
Petra M Nederlof ◽  
Gerrit K J Hooijer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Gene Amplification ◽  
In Situ Hybridisation ◽  
Gene Copy ◽  
Test Results ◽  
Her2 Gene ◽  
Gene Copies ◽  
Her2 Gene Amplification ◽  
Test Result

AimsEquivocal human epidermal growth factor receptor 2 protein (HER2) (2+) immunohistochemistry (IHC) is subject to significant interobserver variation and poses a challenge in obtaining a definitive positive or negative test result. This equivocal test result group accounts for approximately 15% of all tumours, and for optimal guidance of HER2 targeted therapy, a further analysis of quantification of gene copy number and amplification status is needed for patients with early or metastatic breast cancer.Methods553 breast-cancer specimens with equivocal HER2 IHC(2+) test results were collected and subsequently centrally retested by chromogenic in situ hybridisation (CISH), and HER2 gene copy numbers per tumour cell nucleus were determined.ResultsUsing CISH, 77 of 553 equivocal HER2 IHC(2+) test result cases (13.9% of total) showed high levels of HER2 gene amplification (≥10.0 gene copies per nucleus), and 41 of 553 (7.4% of total) showed low-level HER2 gene amplification (6.0–9.9 gene copies per nucleus). In 73.6% of cases, no amplification of the HER2 gene was shown, and in only 4.9% of cases was an equivocal test result by CISH observed (4.0–5.9 gene copies per nucleus).ConclusionsTesting by CISH of all equivocal HER2 IHC(2+) test result provides a definitive guidance in HER2 targeted therapy in 95.1% of cases. A significant proportion (21.3%) of patients with equivocal IHC(2+) test results show amplification of the HER2 gene.

Comparison of Pathvysion and Poseidon HER2 FISH assays in measuring HER2 amplification in breast cancer: a validation study

2009 ◽  
Vol 63 (4) ◽  
pp. 341-346 ◽  
Author(s):  
Monika Francz ◽  
Kristof Egervari ◽  
Laszlo Kardos ◽  
Judit Toth ◽  
Zoltan Nemes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Validation Study ◽  
Predictive Value ◽  
In Situ Hybridisation ◽  
Correlation Coefficients ◽  
Fluorescence In Situ Hybridisation ◽  
Her2 Gene ◽  
Perfect Agreement ◽  
Diagnostic Facility

AimsThe current study was done as a validation study prior to setting up a clinical HER2 testing service using the new commercial Poseidon HER2 fluorescence in situ hybridisation (FISH) assay. However, it was felt that the experience of the authors of this study may be of interest to other laboratories when considering setting up a HER2 diagnostic facility.Methods122 patients who had been diagnosed with invasive breast cancer were selected. Immunolabelling with HercepTest, PathVysion and Poseidon FISH assays were carried out using tissue microarray blocks.ResultsConcordance correlation coefficients showed near perfect agreement in average HER2 and centromere specific signal counts per cell and in the HER2/CEP17 ratios between the PathVysion and the Poseidon FISH assays. In addition, the κ measure showed perfect agreement (κ 0.9441, p<0.0001), and if only 2+ cases were considered there was substantial agreement (κ 0.7671, p=0.0006), between the two assays. The sensitivity and the specificity of the Poseidon FISH kit were calculated to be 95.2% and 100%, respectively, whereas the positive predictive value (PPV) and negative predictive value (NPV) were 100% and 99%, respectively. With regard to the ability to presume HER2 polysomy, the Poseidon FISH kit had a sensitivity of 93.3% and a specificity of 99.1%, with PPV and NPV of 93.3% and 99.1%, respectively, as assessed with PathVysion classification as the reference.ConclusionsStatistical analysis confirmed that the two FISH assays are comparable in terms of detection of HER2 gene amplification. Proceeding from these findings, the genetic diagnoses obtained with the Poseidon kit can be considered to be as valuable as the results from the Food and Drug Administration approved PathVysion assay, and its utilisation in routine HER2 diagnostics is proposed.

scholarly journals Sequential HER2 blockade as effective therapy in chemorefractory, HER2 gene-amplified, RAS wild-type, metastatic colorectal cancer: learning from a clinical case

ESMO Open ◽  
2018 ◽  
Vol 3 (1) ◽  
pp. e000299 ◽  
Author(s):  
Erika Martinelli ◽  
Teresa Troiani ◽  
Vincenzo Sforza ◽  
Giulia Martini ◽  
Claudia Cardone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Gene Amplification ◽  
Clinical Case ◽  
In Situ Hybridisation ◽  
Fluorescence In Situ Hybridisation ◽  
Cancer Resistance ◽  
Wild Type ◽  
Her2 Gene ◽  
Her2 Gene Amplification

BackgroundConstitutive activation of HER2-dependent intracellular signalling by HER2 gene amplification or by HER2 mutations has been demonstrated as a mechanism of primary and secondary cancer resistance to cetuximab or panitumumab in preclinical and clinical models of metastatic colorectal cancer (mCRC). Both HER2 Amplification for Colorectal Cancer Enhanced Stratification (HERACLES) cohort A and My Pathway clinical trials provided clinical evidence that anti-HER2 therapies could be active in these patients.Patient and methodsHER2 gene amplification and HER2 protein overexpression analysis were performed in tumour tissue by fluorescence in situ hybridisation and immunohistochemistry. HER2 positivity was defined according to HERACLES CRC-specific HER2 scoring criteria. DNA analysis for multiple assessment of gene mutations or amplifications was carried out with the next-generation sequencing (NGS) Ion AmpliSeq Colon and Lung Cancer Panel and by using a more extensive targeted high-multiplex PCR-based NGS panel (OncoMine Comprehensive Assay).ResultsWe report the clinical case of a patient with HER2 gene amplified and RAS/BRAF wild-type mCRC who experienced a long lasting and relevant clinical efficacy from sequential anti-HER2 therapies (trastuzumab plus lapatinib, pertuzumab plus trastuzumab, trastuzumab emtansine, trastuzumab plus capecitabine) achieving a cumulative clinical benefit of 29 months, after failure of the first three lines of standard treatments, which included all the potentially active drugs in mCRC, and which accounted for only 14 months of disease control. HER gene amplification was confirmed by NGS on two different metastatic lesions during the evolution of the disease.ConclusionThe clinical case highlights the role of HER2 gene amplification as a key genetic driver of cancer development and progression in mCRC and suggests that sequential HER2 blockade could be a potential therapeutic strategy.

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