Chromogenic in situ hybridization in examination of HER2 amplification status in breast cancer specimens with weak HER2 expression

2010 ◽  
Vol 30 (10) ◽  
pp. 1141-1143
Author(s):  
Chen-guang BAI ◽  
Can-rong NI ◽  
Li-yang TAO ◽  
Wei-qiang ZHENG ◽  
Da-lie MA
Keyword(s):  
Breast Cancer ◽  
Her2 Expression ◽  
Her2 Amplification

scholarly journals Novel markers to detect HER2 amplification in Breast cancer

2021 ◽  
Author(s):  
Shikha Mudgal ◽  
Arnav Kalra ◽  
Shalinee Rao ◽  
Bina Ravi ◽  
Nilotpal Chowdhury
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Predictive Biomarker ◽  
Gene Expression Omnibus ◽  
Surrogate Markers ◽  
Her2 Expression ◽  
Her2 Amplification ◽  
Reflex Testing ◽  
Geo Database

Overexpression of HER2 in breast cancer is an important prognostic and predictive biomarker, assessed using immunohistochemistry (IHC) and in situ hybridization (ISH). More than 20% of tumours are graded equivocal on IHC and is send for reflex testing via ISH. In situ hybridization (ISH) is an expensive assay and is not available widely in resource limiting areas. Therefore, we propose that genes found significantly co-expressed with HER2 in breast cancer can be used as surrogate markers for HER2 in breast cancer which can detect HER2 positivity on IHC itself. This hypothesis is based on analysis of publicly available datasets from the Gene Expression Omnibus (GEO) database. The genes found most significantly correlated with HER2 expression were PGAP3 (r = 0.85), GRB7 (r = 0.82), STARD3 (r = 0.78), CDK12 (r= 0.68), PSMD3 (r= 0.67) and GSDMB (r = 0.63). We hypothesize that these identified surrogate markers for HER2 amplification which can be detected on IHC can detect HER2 amplification status in HER2 equivocal tumors based on IHC staining alone and will reduce the number of HER2 2+ (equivocal) category tumours.

Establishment of the Australian In Situ Hybridization Program for the Assessment of HER2 Amplification in Breast Cancer

2010 ◽  
Vol 19 (4) ◽  
pp. 187-193 ◽  
Author(s):  
Gelareh Farshid ◽  
Jane E. Armes ◽  
Richard Bell ◽  
Margaret Cummings ◽  
Stephen Fox ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Her2 Amplification

scholarly journals Evaluating HER2 Gene Amplification Using Chromogenic In Situ Hybridization (CISH) Method In Comparison To Immunohistochemistry Method in Breast Carcinoma

2018 ◽  
Vol 6 (11) ◽  
pp. 1977-1981 ◽  
Author(s):  
Hadi Atabati ◽  
Amir Raoofi ◽  
Abdollah Amini ◽  
Reza Masteri Farahani
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Gene Amplification ◽  
Method Comparison ◽  
Her2 Expression ◽  
Her2 Gene ◽  
Cross Sectional ◽  
Exact Test ◽  
Chromogenic In Situ Hybridization

BACKGROUND: In patients with breast cancer, HER2 gene expression is of a great importance in reacting to Herceptin treatment. To evaluate this event, immunohistochemistry (IHC) has been done routinely on the basis of scoring it and so the patients were divided into 4 groups. Lately, as there have been disagreements about how to treat score 2 patients, chromogenic in situ hybridization (CISH) and florescence in situ hybridization (FISH) are introduced. Since CISH method is more convenient than FISH for gene amplification study, FISH has been substituted by CISH. AIM: The current study is conducted in order to investigate whether using CISH is a better method comparison to IHC method for determines HER2 expression in patients with breast cancer in. METHODS: In this cross-sectional descriptive analytical study, information of 44 female patients with invasive ductal breast cancer were gathered from Imam Reza and Omid Hospital in Mashhad. IHC staining was done for all patients in order to determine the level of HER2 expression, and after scoring them into 4 groups of 0, +1, +2 and +3, CISH staining was carried out for all 4 groups. At the end, results from both methods were statistically evaluated using SPSS software V.22.0. RESULTS: The average age of patients was 50.2 with the standard deviation of 10.96. Using IHC method was observed that 2.6% (1 patient), 26.3% (10 patients), 65.8% (25 patients) and 5.3% (2 patients) percentage of patients had scores of 0, +1, +2 and +3. On the other hand, CISH method showed 36 patients (90%) with no amplifications and 4 (10%) with sever amplifications. In a comparative study using Fisher's exact test (p = 0.000), we found a significant relation between IHC method and CISH method indicating that all patients showing severe amplifications in CISH method, owned scores of +2 and +3 in IHC method. CONCLUSION: According to the present study and comparing the results with similar previous studies, it can be concluded that CISH method works highly effective in determining HER2 expression level in patients with breast cancer. This method is also able to determine the status of patients with score +2 in IHC for their treatment with herceptin

scholarly journals Transcriptome and genome evolution during HER2-amplified breast neoplasia

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Peipei Lu ◽  
Joseph Foley ◽  
Chunfang Zhu ◽  
Katherine McNamara ◽  
Korsuk Sirinukunwattana ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Ductal Carcinoma ◽  
Copy Number Variations ◽  
Neoplastic Progression ◽  
Interferon Signaling ◽  
Her2 Amplification ◽  
Cancer Multiple ◽  
Spatially Oriented

Abstract Background The acquisition of oncogenic drivers is a critical feature of cancer progression. For some carcinomas, it is clear that certain genetic drivers occur early in neoplasia and others late. Why these drivers are selected and how these changes alter the neoplasia’s fitness is less understood. Methods Here we use spatially oriented genomic approaches to identify transcriptomic and genetic changes at the single-duct level within precursor neoplasia associated with invasive breast cancer. We study HER2 amplification in ductal carcinoma in situ (DCIS) as an event that can be both quantified and spatially located via fluorescence in situ hybridization (FISH) and immunohistochemistry on fixed paraffin-embedded tissue. Results By combining the HER2-FISH with the laser capture microdissection (LCM) Smart-3SEQ method, we found that HER2 amplification in DCIS alters the transcriptomic profiles and increases diversity of copy number variations (CNVs). Particularly, interferon signaling pathway is activated by HER2 amplification in DCIS, which may provide a prolonged interferon signaling activation in HER2-positive breast cancer. Multiple subclones of HER2-amplified DCIS with distinct CNV profiles are observed, suggesting that multiple events occurred for the acquisition of HER2 amplification. Notably, DCIS acquires key transcriptomic changes and CNV events prior to HER2 amplification, suggesting that pre-amplified DCIS may create a cellular state primed to gain HER2 amplification for growth advantage. Conclusion By using genomic methods that are spatially oriented, this study identifies several features that appear to generate insights into neoplastic progression in precancer lesions at a single-duct level.

HER2 amplification through CISH -chromogenic hybridization in situ- on breast cancer Her 2 2+ by immunohistochemistry -ICH

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 22147-22147
Author(s):  
S. R. Bella ◽  
D. Lerda ◽  
A. Guidi ◽  
R. Theaux ◽  
L. Armando ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Her2 Amplification ◽  
Her 2 ◽  
Hybridization In Situ

Next-generation sequencing (NGS) identifies a new breast cancer subtype with HER2 low-amplification status as a candidate for targeted therapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 553-553
Author(s):  
Guo-Chun Zhang ◽  
Ning Liao ◽  
Bo Chen ◽  
Jiali Lin ◽  
Jianguo Lai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Copy Number ◽  
Breast Cancer Subtype ◽  
Metastatic Breast ◽  
Receiver Operating Curve ◽  
Her2 Status ◽  
Her2 Expression ◽  
Her2 Amplification ◽  
Her2 Positive ◽  
Mutation Profile

553 Background: HER2 expression or amplification qualify patients to receive targeted therapeutics against HER2; however, traditional methods of quantifying HER2 amplification using fluorescence in situ hybridization (FISH) do not include a reliable definition for low level amplification. With the promising response rate of patients with low HER2 amplified-metastatic breast cancer to subsequent-line trastuzumab deruxtecan (DS-8201a) therapy, there is a need to improve the existing criteria to accurately identify patients with low HER2. In our study, we investigate whether HER2 amplification quantified by NGS could provide a method to stratify patients into subgroups. Methods: A total of 774 patients diagnosed with breast cancer from Guangdong Provincial People's Hospital (GDPH) who underwent targeted NGS using 520 or 33 cancer-related genes and had their HER2 status evaluated with either FISH or IHC were included in this study. HER2 status were defined as per 2018 ASCO/ACP guidelines. Results: Our results demonstrate that NGS could quantify HER2 amplification with high sensitivity and specificity, with area under the curve of 0.990 [95%CI: 0.982-0.999]. The receiver operating curve indicated an optimal cut-off of 2.62 copy number (CN) for identifying IHC/FISH HER2-negative status with 97.8% specificity. Meanwhile, the cut-off of ≥ 3.62 CN identified patients with IHC/FISH HER2-positive status with 99.8% specificity. Among the 774 patients, 65.8% (n = 509) had HER2 CN of ≤ 2.62 and were classified as HER2 non-amplified, while 25.8% (n = 199) had HER2 CN of ≥ 3.62, classified as HER2-amplified. The remaining 66 patients (8.5%) had HER2 CN between 2.62 and 3.62, and were the patients with heterogeneous IHC/FISH results, classified using NGS as HER2 low-amplified. Patients with low-amplified (49.0% vs. 38.8%, P < 0.001) and amplified (50.3% vs. 38.8%, P < 0.001) HER2 had significantly more number of copy number amplifications in other gene, including CDK12, RARA, and SPOP (P < 0.001, P < 0.001) than patients with HER2 non-amplified, indicating distinct mutation profile. Conclusions: Our results demonstrate that NGS could provide a more accurate stratification of patients based on their HER2 amplification levels. Patients with low levels of HER2 amplification has a distinct mutation profile, suggesting that NGS could serve as a robust tool to identify patients with HER2 amplification, whether high or low, who could benefit treatment with targeted agents designed against heterogeneous HER2 expression.

scholarly journals In situ single-cell analysis identifies heterogeneity for PIK3CA mutation and HER2 amplification in HER2-positive breast cancer

2015 ◽  
Vol 47 (10) ◽  
pp. 1212-1219 ◽  
Author(s):  
Michalina Janiszewska ◽  
Lin Liu ◽  
Vanessa Almendro ◽  
Yanan Kuang ◽  
Cloud Paweletz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Pik3ca Mutation ◽  
Cell Analysis ◽  
Her2 Amplification ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

scholarly journals Evaluation of HER2 by Automated FISH and IHC in Gastric Carcinoma Biopsies

2016 ◽  
Vol 31 (1) ◽  
pp. 38-43 ◽  
Author(s):  
Maria R. Silva ◽  
Ana Alarcão ◽  
Teresa Ferreira ◽  
Maria d'Aguiar ◽  
Ana Ladeirinha ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Intestinal Type ◽  
Diffuse Type ◽  
Her2 Expression ◽  
Her2 Amplification ◽  
Bond System ◽  
Routine Procedures ◽  
Dual Probe ◽  
Her2 Positivity

Purpose The use of trastuzumab (Herceptin) to target HER2 has been applied in breast carcinoma and gastric carcinoma (GC). Previous studies have tested trastuzumab's effectiveness by assessing HER2 expression or HER2 amplification by means of immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). In this work we aimed to evaluate automated FISH and IHC technologies for HER2 detection in GC biopsies to be used in routine pathology practice. Methods The study used an Oracle HER2 IHC System and an LSI HER2/CEP17 Dual Probe on an automated Bond™ system (Leica Microsystems). One hundred GC biopsies were evaluated including 44 intestinal type, 38 diffuse type and 18 indeterminate type according to Lauren's classification. Results The overall concordance rate between the automated FISH and IHC methods was 94% ( κ = 0.87), as 6 samples were scored as equivocal (4 in IHC and 2 in FISH). Moreover, HER2 positivity was significantly different between the 3 types of GC (p<0.05), being more frequent in intestinal-type GC (23%) than in the other 2 histological types (5% and 0%). Finally, the HER2/CEP17 FISH ratio was significantly different (p<0.01) between disomic and polysomic samples, being higher in polysomic samples (mean 1.633 ± 0.509) than in disomic samples (mean 1.231 ± 0.675). Conclusions Automated HER2 testing of GC biopsies using the Leica Bond system was useful and efficient. This method allowed us to improve normal routine procedures, minimizing time and costs as well as handling and observation errors.

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