The INFORM HER2 Dual ISH assay compared with FISH to determine HER2 gene status in invasive breast carcinoma.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 25-25
Author(s):  
I. R. Loftin ◽  
A. McElhinny ◽  
R. Miller ◽  
C. Garcia ◽  
I. Bai ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Light Microscopy ◽  
Method Comparison ◽  
Invasive Breast Carcinoma ◽  
Chromosome 17 ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Central Laboratory ◽  
Her2 Gene ◽  
Reproducibility Study

25 Background: The HER2 gene, located on chromosome 17 (Chr17), is amplified in 15-25% of patients with invasive breast carcinoma. Amplification and/or HER2 overexpression is associated with poor clinical outcome for these patients; however prognosis is improved if HER2 status indicates eligibility of patients for trastuzumab therapy. Thus, accurate diagnosis of HER2 status through a companion diagnostic is essential. Here we validated the INFORM HER2 Dual ISH Probe Cocktail (Dual ISH) assay as an alternative to FISH, the current gold standard for HER2 testing. The Dual ISH assay is fully automated and is scored using light microscopy. Methods: A multi-site method comparison and inter-laboratory reproducibility study were performed. 5 sites were used to compare Dual ISH results with FISH (Vysis PathVysion). 510 invasive breast carcinoma cases were stained at 3 clinical sites, FISH staining was performed at a fourth site (central laboratory). IHC status was determined at a fifth site (second central laboratory). In addition, 6 cases were evaluated for inter-site (3 sites), inter-reader (6 readers), inter-run (15 runs) and intra-run (duplicate slides) reproducibility. All assay steps were fully automated on a VENTANA BenchMark XT automated slide stainer, using a HER2 repeat-reduced, dinitrophenyl-labeled probe targeting the HER2 gene, detected with silver metallographic detection, and a digoxigenin-labeled Chr 17 probe, detected by an alkaline phosphatase-driven red chromogenic detection. HER2 and CHR17 signals were enumerated using conventional light microscopy allowing interpretation within the morphological context of the specimen. HER2 status was determined as the ratio of HER2/Chr17, where a ratio <2 is non-amplified and a ratio ≥2 is amplified. Results: The positive and negative agreement rates with FISH (95% CI) were 96% (92.6-97.9) and 92.3% (88.6-94.8), respectively. The HER2 Dual ISH assay also was highly reproducible in determining HER2/Chr17 ratio across sites, days, readers and runs. Conclusions: The fully automated INFORM HER2 Dual ISH assay is reproducible and concordant with the manual FISH assay in determining HER2 status in invasive breast carcinoma.

Clinical role of HER2 gene amplification and chromosome 17: a study on 154 IHC-equivocal cases of invasive breast carcinoma patients

Tumor Biology ◽  
2016 ◽  
Vol 37 (7) ◽  
pp. 8665-8672 ◽  
Author(s):  
Muhammad Afzal ◽  
Mohammed Amir ◽  
Muhammad Jawad Hassan ◽  
Muhammad Sikander Hussain ◽  
Muhammad Naveed Aziz ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Gene Amplification ◽  
Invasive Breast Carcinoma ◽  
Chromosome 17 ◽  
Her2 Gene ◽  
Clinical Role ◽  
Her2 Gene Amplification

STUDY ON HER2 STATUS AND RELATIONSHIP WITH PROGNOSTIC FACTORS IN INVASIVE BREAST CARCINOMA

2018 ◽  
Vol 8 (4) ◽  
pp. 13-22
Author(s):  
Thuan Dang Cong ◽  
Lan Le Trong ◽  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Gene Amplification ◽  
Molecular Subtypes ◽  
Invasive Breast Carcinoma ◽  
Disease Stage ◽  
Her2 Status ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Her2 Gene Amplification

Background: To select patients with targeted breast cancer need to accurately determine the status of HER2 gene amplification. Therefore, HER2 gene amplification should be determined by in situ hybridization (ISH) for all of cases which HER2 positive (2+) by Immunohistochemistry (IHC) staining. Our study aims to apply IHC and DISH to detect HER2 status and relationship with prognostic factors in breast cancer. Subjects and research methods: Cross-sectional descriptive study; 92 patients were diagnosed with invasive breast carcinoma at Hue University Hospital and Hue Central Hospital. IHC and DISH are performed on the Benchmark machines (Ventana) of Roche Diagnostics. Molecular subtypes based on the classification of Saint Gallen (2011). Results: Tumor is usually located in the right breast (53.3%); tumor size > 2-5cm (46.7%); Invasive carcinoma not otherwise specified (73.9%); lymph node metastasis 59.8%, histologic grade 2 (60.3%); disease stage II (51.1%). ER (+) 42.4%, PR (+) 41.3%, HER2 (+) 34.8%, Ki67 (+) 59.8% of cases. The most common molecular subtype of breast cancer is Luminal B (28.3%). HER2 gene amplified by DISH in HER2 (2+) 46.2%, HER2 (3+) by 100%. HER2 gene amplification is associated with HER2 protein expression, molecular subtypes; There is no relationship with the disease stage. Conclusion: In addition to immunohistochemistry, gene amplification with DISH is useful for determining the status of the HER2 gene and supporting the accurate grouping molecular subtypes of breast cancer and target therapy. 34.8% HER2 positive by IHC staining; HER2 gene amplified by DISH in 46.2% of HER2 (2+) cases. There are relationship between the HER2 gene amplified and HER2 protein expression, molecular subtypes in invasive breast carcinoma. Key words: invasive breast cancer, immunohistochemistry, histologic grade, disease stage, molecular subtypes, Dual In Situ Hybridization, DISH

Use of HER2 score correction for putative chromosome 17 (Chr-17) aneusomy to increase eligibility for anti-HER2 therapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 620-620
Author(s):  
Eugen C. Minca ◽  
Bryce P. Portier ◽  
Zhen Wang ◽  
Christopher Lanigan ◽  
G. Thomas Budd ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Health System ◽  
Significant Proportion ◽  
Cleveland Clinic ◽  
Case Series ◽  
Chromosome 17 ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Consecutive Series ◽  
Reference Probe

620 Background: HER2 amplification or overexpression status directs therapy choice in breast carcinoma. HER2/Chr-17 ratio is commonly assessed by fluorescence in-situ hybridization (FISH) using a CEP17 centromeric reference probe and ASCO/CAP scoring criteria. However, α-centromeric reference probes may underestimate true HER2 status in cases with para-centromeric amplification. Here we present comprehensive algorithmic testing of an alternative Chr-17 reference locus for resolution of putative CEP17-aneusomic cases in a consecutive series, within a single health system. Methods: 150 of 1256 consecutive breast carcinoma cases accessioned in 2011 within the Cleveland Clinic Health System displayed a mean CEP17 copy number greater than 3.0 by FISH (aneusomy). The patients were reflex-HER2 tested by FISH with a reference probe for the D17S122 locus (17p12) and a corrected HER2/Chr-17 ratio was calculated. Cases with equivocal HER2/D17S122 ratio (1.8-2.2) were further reflex tested for HER2 overexpression by immunohistochemistry (IHC). Results: Of 117 initially non-amplified cases by HER2/CEP17, 20 (17%) were revised to amplified and 18 (15.3%) to equivocal by HER2/D17S122. Of 3 initially equivocal cases, 1 was revised to amplified and 1 remained equivocal. Of the 19 equivocal cases by HER2/D17S122, 3 were revised to positive by IHC. Overall, for CEP17 aneusomic cases tested using this algorithmic approach, 24 of 120 (20%) patients with initial non-amplified or equivocal HER2 status became eligible for anti-HER2-based therapy, which was also considered in 10 equivocal cases with a HER2/D17S122 ratio of 2.0 - 2.2. A significantly lower proportion of initially amplified cases was revised as non-amplified by HER2/D17S122 (1 of 30, 3.3%, p<0.05). Conclusions: Our data, collected within a single health system for a consecutive case series, underscores the clinical limitations of commonly used FISH probes for HER2 testing and demonstrates that algorithmic use of a non-centromeric Chr-17 reference probe alters HER2 status and increases eligibility for anti-HER2 based therapy in a significant proportion of patients.

scholarly journals Erratum to: Clinical role of HER2 gene amplification and chromosome 17: a study on 154 IHC-equivocal cases of invasive breast carcinoma patients

Tumor Biology ◽  
2016 ◽  
Vol 37 (11) ◽  
pp. 15341-15341
Author(s):  
Muhammad Afzal ◽  
Mohammed Amir ◽  
Muhammad Jawad Hassan ◽  
Muhammad Sikander Hussain ◽  
Muhammad Naveed Aziz ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Gene Amplification ◽  
Invasive Breast Carcinoma ◽  
Chromosome 17 ◽  
Her2 Gene ◽  
Clinical Role ◽  
Her2 Gene Amplification

Clinicopathological significance of WT1 expression in invasive breast carcinoma with >90% mucinous component

2021 ◽  
pp. jclinpath-2021-207464
Author(s):  
Xiaoli Xu ◽  
Rui Bi ◽  
Ruohong Shui ◽  
Baohua Yu ◽  
Yufan Cheng ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Growth Pattern ◽  
Histological Grade ◽  
Invasive Breast Carcinoma ◽  
Nuclear Grade ◽  
Proliferation Index ◽  
Her2 Overexpression ◽  
Ki 67 ◽  
Mucinous Component ◽  
Clinicopathological Significance

AimsThis study was aimed to investigate the clinicopathological significance of immunohistochemical (IHC) Wilm’s tumour 1 (WT1) expression in invasive breast carcinoma with >90% mucinous components.MethodsOne hundred specimens of invasive breast carcinoma with >90% mucinous component were collected. All H&E-stained slides were reviewed, and the clinicopathological data, including sex, age, tumour size, nuclear grade, histological grade, growth pattern and lymph node (LN) status, were collected. IHC staining of WT1, oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 was performed. Fluorescence in situ hybridisation was used to verify the amplification of the HER2 gene. The relationship between WT1 expression and clinicopathological features was analysed statistically.ResultsWT1 expression was detected in 67% (67/100) of invasive breast carcinoma with >90% mucinous components. WT1 expression was significantly associated with low-to-intermediate nuclear grade/histological grade, ER and PR positivity, HER2 negativity, Ki-67 proliferation index <30% and noLN metastasis (all p<0.001). Micropapillary architecture was observed in 80% of cases. WT1 expression was not significantly correlated with different percentage of micropapillary components (p=0.422). None of the histological grade 3 tumours, tumours with HER2 overexpression/amplification and triple-negative specimens showed WT1 expression.ConclusionsWT1 expression was significantly related with low-intermediate nuclear/histological grade, ER positivity, HER2 negativity, a lower Ki-67 proliferation index and no LN metastasis in invasive breast carcinoma with >90% mucinous component. The micropapillary growth pattern in this type of tumour did not show a specific relationship with WT1 expression.

Chromosome 17 Aneusomy is Associated with Poor Prognostic Factors in Invasive Breast Carcinoma

2003 ◽  
Vol 77 (2) ◽  
pp. 109-114 ◽  
Author(s):  
A.D. Watters ◽  
J.J. Going ◽  
T.G. Cooke ◽  
J.M.S. Bartlett
Keyword(s):  
Prognostic Factors ◽  
Breast Carcinoma ◽  
Invasive Breast Carcinoma ◽  
Chromosome 17

HER2 status testing by immunohistochemical and fFluorescence in situ hybridization in China

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22233-e22233
Author(s):  
W. Tao ◽  
J. Zefei ◽  
Z. Xuan ◽  
L. Xiaobing ◽  
Z. Shaohua ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Her2 Status ◽  
Central Laboratory ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Clinical Prognosis ◽  
Her2 Testing ◽  
Regional Laboratory

e22233 Background: HER2 gene overexpression is associated with aggressive breast cancer and poor clinical prognosis. Humanized anti-HER2 monoclonal antibody trastuzumab, which is targeted HER2 protein has showed to improve overall survival in patients with HER2-positive breast cancer in both the metastatic and adjuvant settings. There are some differences in HER2 positive rate among difference reports in China. This study tested HER2 status by immunohistochemistry(IHC) and fluorescence in situ hybridization (FISH) and compared HER2 testing at central and regional laboratories in China. Methods: Assessment of HER2 status was performed by FISH using the HercepTeast kit at central laboratory and by IHC using commercial available anti-HER2 probe in formalin-fixed and paraffin-embedded tissue section of 280 breast cancer samples. IHC HER2 testing was performed on 149 samples in the central laboratory. IHC HER2 testing was performed on 80 samples at both central laboratory and regional laboratory. Results: 280 samples were tested 373 times testing by IHC and FISH. The results were showed in table 1 . 80 samples was tested by IHC at central and regional laboratory and testing results of 36.4% samples were accordant (K=0.038). 94.1% IHC3+ at central laboratory were HER2 FISH positive and 83.3% IHC 3+ at regional laboratory were HER2 FISH positive. 86.7% IHC 2+ at central laboratory were HER2 FISH positive and 62.7% IHC 2+ at regional laboratory were HER2 FISH positive. 17 samples were observed HER2 FISH positive in the 27 IHC 0/1+ tested at regional laboratoty. So good correlation was obsearved between FISH HER2 status and IHC results from central laboratory but not from regional laboratory. Conclusions: This study emphasized the important of accurate HER2 testing. HER2 FISH test should be performed for the IHC 2+ samples. Even HER2 FISH test maybe performed for IHC 0/1 sample according to clinical characteristics in China in order to make the patients have targeted therapy chance. [Table: see text] No significant financial relationships to disclose.

scholarly journals Poor prognostic significance of unamplified chromosome 17 polysomy in invasive breast carcinoma

2009 ◽  
Vol 22 (8) ◽  
pp. 1044-1048 ◽  
Author(s):  
Uma Krishnamurti ◽  
Jennifer L Hammers ◽  
Folefac D Atem ◽  
Patrick D Storto ◽  
Jan F Silverman
Keyword(s):  
Breast Carcinoma ◽  
Prognostic Significance ◽  
Invasive Breast Carcinoma ◽  
Chromosome 17

scholarly journals HER2 Protein Overexpression and Gene Amplification in Plasmacytoid Urothelial Carcinoma of the Urinary Bladder

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Bohyun Kim ◽  
Gilhyang Kim ◽  
Boram Song ◽  
Cheol Lee ◽  
Jeong Hwan Park ◽  
...  
Keyword(s):  
Protein Expression ◽  
Urothelial Carcinoma ◽  
Gene Amplification ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Supporting Evidence ◽  
Protein Overexpression ◽  
Her2 Gene ◽  
Her2 Protein ◽  
Urothelial Carcinomas

Aim. HER2 overexpression has been reported in a minority of urothelial carcinomas, but little is known about HER2 protein expression and gene alterations in plasmacytoid urothelial carcinoma, a rare and aggressive variant. The aim of this study was to clarify the HER2 status in plasmacytoid urothelial carcinomas.Methods. Six cases of plasmacytoid urothelial carcinoma were included, in which we evaluated HER2 protein expression by immunohistochemistry (IHC) andHER2gene amplification by fluorescencein situhybridization (FISH).Results. The patients’ ages ranged from 57 to 83 years (mean age, 71 years). Five patients were male and one was female. The ratio of the plasmacytoid component ranged from 30% to 100% (mean, 77%). HER2 expression score was 3+ in 4 cases, 2+ in one case, and negative in one case. HER2 gene amplification was positive in 3 cases, of which 2 cases showed a 3+ HER2 IHC score but one case was negative for HER2 IHC. Another 2 cases showed equivocal HER2 FISH results, and one remaining case was negative for HER2 FISH.Conclusion. Our observation that plasmacytoid urothelial carcinomas frequently demonstrated HER2 protein overexpression provides supporting evidence that HER2 may be a potential therapeutic target for plasmacytoid urothelial carcinoma.

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