Abstract P5-02-05: Assessment of HER2 status in invasive breast cancer with increased centromere 17 copy number by fluorescence in situ hybridization

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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Comparison of HER2 Status by Fluorescence in Situ Hybridization and Immunohistochemistry to Predict Benefit From Dose Escalation of Adjuvant Doxorubicin-Based Therapy in Node-Positive Breast Cancer Patients

Journal of Clinical Oncology ◽

10.1200/jco.2005.11.012 ◽

2005 ◽

Vol 23 (19) ◽

pp. 4287-4297 ◽

Cited By ~ 76

Author(s):

Lynn G. Dressler ◽

Donald A. Berry ◽

Gloria Broadwater ◽

David Cowan ◽

Kelly Cox ◽

...

Keyword(s):

Breast Cancer ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Cancer Patients ◽

Her2 Status ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Node Positive ◽

Positive Breast Cancer

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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Abnormal Chromosome 8 Copy Number in Stage I to Stage IV Breast Cancer Studied by Fluorescence In Situ Hybridization

Cancer Genetics and Cytogenetics ◽

10.1016/s0165-4608(98)00112-5 ◽

1999 ◽

Vol 108 (1) ◽

pp. 1-5 ◽

Cited By ~ 13

Author(s):

Hon Fong L Mark ◽

William Taylor ◽

Stephen Brown ◽

Mangala Samy ◽

Ci-Lin Sun ◽

...

Keyword(s):

Breast Cancer ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Copy Number ◽

Stage Iv ◽

Chromosome 8 ◽

Stage I ◽

Abnormal Chromosome ◽

Stage Iv Breast Cancer

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Comparative Performance of Breast Cancer Human Epidermal Growth Factor Receptor 2 Fluorescence In Situ Hybridization and Brightfield In Situ Hybridization on College of American Pathologists Proficiency Tests

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2017-0457-cp ◽

2018 ◽

Vol 142 (10) ◽

pp. 1254-1259 ◽

Cited By ~ 1

Author(s):

Katherine B. Geiersbach ◽

Julia A. Bridge ◽

Michelle Dolan ◽

Lawrence J. Jennings ◽

Diane L. Persons ◽

...

Keyword(s):

Breast Cancer ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Proficiency Testing ◽

Copy Number ◽

Fish Analysis ◽

Proficiency Tests ◽

Comparative Performance ◽

Significant Difference

Context.— Fluorescence in situ hybridization (FISH) and brightfield in situ hybridization (ISH) are 2 clinically approved laboratory methods for detecting ERBB2 (HER2) amplification in breast cancer. Objective.— To compare the performance of FISH and brightfield ISH on proficiency testing administered by the College of American Pathologists Laboratory Accreditation Program. Design.— Retrospective review was performed on 70 tissue core samples in 7 separate proficiency testing surveys conducted between 2009 and 2013. Results.— The samples included 13 consensus-amplified tissue cores, 53 consensus-nonamplified cores, and 4 cores that did not reach consensus for FISH and/or brightfield ISH. There were 2552 individual responses for FISH and 1871 individual responses for brightfield ISH. Consensus response rates were comparable for FISH (2474 of 2524; 98.0%) and brightfield ISH (2135 of 2189; 97.5%). The FISH analysis yielded an average HER2 copy number per cell that was significantly higher (by 2.86; P = .02) compared with brightfield ISH for amplified cores. For nonamplified cores, FISH yielded slightly, but not significantly, higher (by 0.17; P = .10) HER2 copy numbers per cell. There was no significant difference in the average HER2 to control ratio for either consensus-amplified or consensus-nonamplified cores. Participants reported “unable to analyze” more frequently for brightfield ISH (244 of 2453; 9.9%) than they did for FISH (160 of 2684; 6.0%). Conclusions.— Our study indicates a high concordance rate in proficiency testing surveys, with some significant differences noted in the technical performance of these assays. In borderline cases, updated American Society of Clinical Oncology/College of American Pathologists cutoff thresholds that place greater emphasis on HER2 copy number per cell could accentuate those differences between FISH and brightfield ISH.

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