Dual color chromogenic in situ hybridization for determination of HER2 status in breast cancer: a large comparative study to current state of the art fluorescence in situ hybridization

Purpose HER2 is a clinically important tumor marker in breast cancer; however, there is controversy regarding which method reliably measures HER2 status. We compared three HER2 laboratory methods: immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR), to predict disease-free survival (DFS) and overall survival (OS) after adjuvant doxorubicin-based therapy in node-positive breast cancer patients. Methods This is a Cancer and Leukemia Group B (CALGB) study, using 524 tumor blocks collected from breast cancer patients registered to clinical trial CALGB 8541. IHC employed CB11 and AO-11-854 monoclonal antibodies; FISH used PathVysion HER2 DNA Probe kit; PCR utilized differential PCR (D-PCR) methodology. Results Cases HER2 positive by IHC, FISH and D-PCR were 24%, 17%, and 18%, respectively. FISH and IHC were clearly related (κ = 64.8%). All three methods demonstrated a similar relationship for DFS and OS. By any method, for patients with HER2-negative tumors, there was little or no effect of dose of adjuvant doxorubicin-based therapy. For patients with HER2-positive tumors, all three methods predicted a benefit from dose-intense (high-dose) compared with low- or moderate-dose adjuvant doxorubicin-based therapy. Conclusion FISH is a reliable method to predict clinical outcome following adjuvant doxorubicin-based therapy for stage II breast cancer patients. There is a moderate level of concordance among the three methods (IHC, FISH, PCR). None of the methods is clearly superior. Although IHC-positive/FISH-positive tumors yielded the greatest interaction with dose of therapy in predicting outcome, no combination of assays tested was statistically superior.

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Differential prognostic value of positive HER2 status determined by immunohistochemistry or fluorescence in situ hybridization in breast cancer

Breast Cancer Research and Treatment ◽

10.1007/s10549-020-05772-6 ◽

2020 ◽

Vol 183 (2) ◽

pp. 311-319 ◽

Cited By ~ 1

Author(s):

Albina Stocker ◽

Andreas Trojan ◽

Constanze Elfgen ◽

Marie-Louis Hilbers ◽

Linda Moskovszky ◽

...

Keyword(s):

Breast Cancer ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Prognostic Value ◽

Her2 Status

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Comparative Study between Quantitative Digital Image Analysis and Fluorescence In Situ Hybridization of Breast Cancer Equivocal HER2 2+ Cases

Analytical Cellular Pathology ◽

10.1155/2014/608254 ◽

2014 ◽

Vol 2014 ◽

pp. 1-1

Author(s):

E. Ayad ◽

M. Mansy ◽

D. Elwi ◽

M. Salem ◽

M. Salama ◽

...

Keyword(s):

Breast Cancer ◽

Image Analysis ◽

In Situ Hybridization ◽

Comparative Study ◽

Fluorescence In Situ Hybridization ◽

Digital Image ◽

Digital Image Analysis

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HER2 Testing in Invasive Breast Cancer: A Comparison Between Immunohistochemistry and Fluorescence In Situ Hybridization Assays

Research in Molecular Medicine ◽

10.32598/rmm.8.3.1133.1 ◽

2020 ◽

Vol 8 (3) ◽

pp. 139-146

Author(s):

Maryam Moradi Chaleshtori ◽

◽

Zohreh Hojati ◽

Ali Jazaeri ◽

Hossein Teimori ◽

...

Keyword(s):

Breast Cancer ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Gene Amplification ◽

Invasive Breast Cancer ◽

Concordance Rate ◽

Her2 Status ◽

Her2 Gene ◽

Relative Copy Number

Background: HER2 status testing in breast cancer is crucial for the detection of eligible patients for trastuzumab therapy. In this study, the relative copy number of HER2 gene, in patients with breast cancer, was determined by fluorescence in situ hybridization (FISH) and the results were compared with those of immunohistochemistry (IHC) to obtain the concordance rate between these two methods. Material and Methods: HER2 status of 31 invasive breast cancer samples was compared using IHC and FISH techniques. The ratio of HER2/CEP17 was used to determine the amplification of the HER2 gene. If the ratio of HER2/CEP17 is greater than 2.2, HER2 gene amplification has occurred in the cancer cells. Then, a comparative analysis is performed to estimate the concordance rate between FISH and IHC results. Results: The gene amplification of HER2 was observed in 26% of cases by FISH. The IHC and FISH results showed 100%, 36.36%, and 85.71% concordance rates for cases with IHC scores of 3+, 2+, and 0/+1, respectively. The overall concordance between the two methods was 80%. Based on statistical analysis, HER2 status showed a considerable correlation with tumor grade (P= 0.02). No correlation was observed between HER2 gene status and the size and type of tumor, characteristics of lymph node, and patients’ age. Conclusion: The data suggested that IHC results are reliable for HER2 status testing in cases with IHC scores 0/+1 and 3+. However, in patients with an IHC score of +2, it is necessary to perform a complimentary test to evaluate HER2 status to avoid haphazard treatment with trastuzumab in negative cases and identifying positive cases for suitable treatment.

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