Implementation of American Society of Clinical Oncology/College of American Pathologists HER2 Guideline Recommendations in a Tertiary Care Facility Increases HER2 Immunohistochemistry and Fluorescence In Situ Hybridization Concordance and Decreases the Number of Inconclusive Cases

2009 ◽  
Vol 133 (5) ◽  
pp. 775-780 ◽  
Author(s):  
Lavinia P. Middleton ◽  
Kathy M. Price ◽  
Pamela Puig ◽  
Lori J. Heydon ◽  
Emily Tarco ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Clinical Oncology ◽  
Tertiary Care ◽  
Care Facility ◽  
Her2 Testing ◽  
Tertiary Care Facility ◽  
American Society

Abstract Context.—The American Society of Clinical Oncology/ College of American Pathologists (ASCO/CAP) guideline recommendations from January 2007 identified many sources of immunohistochemistry (IHC) testing variation. Objective.—In this current study, we implemented the guidelines and addressed our institution's preanalytic, analytic, and postanalytic variables relating to HER2 testing to improve clinical outcomes. Design.—We evaluated core biopsies performed on breast lesions from 2006 through 2007. Prognostic/predictive markers obtained by IHC were correlated with HER2 fluorescence in situ hybridization (FISH). Preanalytic sources of biopsy testing variation were studied by collecting data on the number of biopsies that needed repeat testing because of inconclusive FISH results. Results.—In the year preceding implementation of the guidelines, the HER2 IHC and FISH concordance was 98%. In an additional 10.8% of cases, the FISH results were inconclusive. When additional material became available to retest the inconclusive cases, the results were informative. Further evaluation of the inconclusive cases revealed that the core needle biopsies received, on average, 4 hours of formalin fixation. After implementation of a minimum 6 hours of fixation and the ASCO/CAP guideline recommendations, the HER2 IHC and FISH concordance was 98.5%. The number of FISH inconclusive cases decreased from 10.8% to 3.4% (a 64% reduction). Repeat estrogen-receptor IHC requests decreased by 40% from 38 in 2006 to 23 in 2007. Conclusions.—We have shown that standardized fixation and adherence to the ASCO/CAP guidelines for HER2 testing has resulted in a greater HER2 IHC and HER2 FISH correlation, decreased numbers of inconclusive FISH cases, decreased repeat estrogen-receptor requests, and financial savings to the Department of Pathology.

A Retrospective Population-Based Comparison of HER2 Immunohistochemistry and Fluorescence In Situ Hybridization in Breast Carcinomas: Impact of 2007 American Society of Clinical Oncology/ College of American Pathologists Criteria

2013 ◽  
Vol 138 (2) ◽  
pp. 213-219 ◽  
Author(s):  
Kurt A. Schalper ◽  
Sudha Kumar ◽  
Pei Hui ◽  
David L. Rimm ◽  
Peter Gershkovich
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Clinical Oncology ◽  
Scoring Systems ◽  
Population Based ◽  
Breast Carcinomas ◽  
Her2 Testing ◽  
Invasive Breast Carcinomas ◽  
American Society

Context.—In 2007 the American Society of Clinical Oncology/College of American Pathologists made new recommendations for HER2 testing and redefined HER2 positivity. Objective.—To analyze results from simultaneous HER2 testing with immunohistochemistry and fluorescence in situ hybridization (FISH) in 2590 invasive breast carcinomas between 2002 and 2010, using 2 scoring systems. Design.—Cases from between 2002 and 2006 were scored by using original US Food and Drug Administration criteria (N = 1138) and those from between 2007 and 2010 were evaluated according to American Society of Clinical Oncology/College of American Pathologists criteria (N = 1452). Concordance between testing methods and clinicopathologic associations were determined. Results.—Overall concordance between immunohistochemistry/FISH in the 9-year period was 96.2% (κ = 0.82), and positive concordance was lower. After 2007, the proportion of HER2/neu-positive and HER2/neu-negative cases was not significantly changed when using immunohistochemistry (10.5% versus 8.9%, P = .22 and 69.4% versus 63%, P = .13, respectively), but the number of equivocal cases was higher (19.9% versus 28%, P < .001). While the proportion of negative cases by FISH remained unchanged after 2007 (86.5% versus 88.2%, P = .76), the number of positive cases was lower (13.4% versus 9.2%, P < .001). In addition, 38 cases (2.6%) were FISH equivocal, 16 of which were also equivocal by immunohistochemistry. Overall, immunohistochemistry/FISH concordance was 95.9% between 2002 and 2006 (κ = 0.82) and 96.4% after 2007 (κ = 0.82). However, an approximately 13% lower positive assay concordance was noted in the last period. Conclusions.—Application of American Society of Clinical Oncology/College of American Pathologists recommendations is associated with comparable overall immunohistochemistry/FISH concordance, reduced positive concordance, and increased equivocal results.

Laboratory Compliance With the American Society of Clinical Oncology/College of American Pathologists Guidelines for Human Epidermal Growth Factor Receptor 2 Testing: A College of American Pathologists Survey of 757 Laboratories

2010 ◽  
Vol 134 (5) ◽  
pp. 728-734
Author(s):  
Raouf E. Nakhleh ◽  
Erin E. Grimm ◽  
Michael O. Idowu ◽  
Rhona J. Souers ◽  
Patrick L. Fitzgibbons
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Clinical Oncology ◽  
Concordance Rate ◽  
Survey Question ◽  
Her2 Testing ◽  
Negative Findings ◽  
Epidermal Growth ◽  
American Society

Abstract Context.—To ensure quality human epidermal growth receptor 2 (HER2) testing in breast cancer, the American Society of Clinical Oncology/College of American Pathologists guidelines were introduced with expected compliance by 2008. Objective.—To assess the effect these guidelines have had on pathology laboratories and their ability to address key components. Design.—In late 2008, a survey was distributed with the HER2 immunohistochemistry (IHC) proficiency testing program. It included questions regarding pathology practice characteristics and assay validation using fluorescence in situ hybridization or another IHC laboratory assay and assessed pathologist HER2 scoring competency. Results.—Of the 907 surveys sent, 757 (83.5%) were returned. The median laboratory accessioned 15 000 cases and performed 190 HER2 tests annually. Quantitative computer image analysis was used by 33% of laboratories. In-house fluorescence in situ hybridization was performed in 23% of laboratories, and 60% of laboratories addressed the 6- to 48-hour tissue fixation requirement by embedding tissue on the weekend. HER2 testing was performed on the initial biopsy in 40%, on the resection specimen in 6%, and on either in 56% of laboratories. Testing was validated with only fluorescence in situ hybridization in 47% of laboratories, whereas 10% of laboratories used another IHC assay only; 13% used both assays, and 12% and 15% of laboratories had not validated their assays or chose “not applicable” on the survey question, respectively. The 90% concordance rate with fluorescence in situ hybridization results was achieved by 88% of laboratories for IHC-negative findings and by 81% of laboratories for IHC-positive cases. The 90% concordance rate for laboratories using another IHC assay was achieved by 80% for negative findings and 75% for positive cases. About 91% of laboratories had a pathologist competency assessment program. Conclusions.—This survey demonstrates the extent and characteristics of HER2 testing. Although some American Society of Clinical Oncology/College of American Pathologists guidelines have been implemented, gaps remain in validation of HER2 IHC testing.

scholarly journals Laboratory Compliance With the American Society of Clinical Oncology/College of American Pathologists Human Epidermal Growth Factor Receptor 2 Testing Guidelines: A 3-Year Comparison of Validation Procedures

2014 ◽  
Vol 138 (7) ◽  
pp. 876-884 ◽  
Author(s):  
Kathryn S. Dyhdalo ◽  
Patrick L. Fitzgibbons ◽  
Jeffery D. Goldsmith ◽  
Rhona J. Souers ◽  
Raouf E. Nakhleh
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Clinical Oncology ◽  
Growth Factor Receptor ◽  
Median Number ◽  
Laboratory Accreditation ◽  
Fixation Time ◽  
Accreditation Program ◽  
American Society

Context.—The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) published guidelines in 2007 regarding testing accuracy, interpretation, and reporting of results for HER2 studies. A 2008 survey identified areas needing improved compliance. Objective.—To reassess laboratory response to those guidelines following a full accreditation cycle for an updated snapshot of laboratory practices regarding ASCO/CAP guidelines. Design.—In 2011, a survey was distributed with the HER2 immunohistochemistry (IHC) proficiency testing program identical to the 2008 survey. Results.—Of the 1150 surveys sent, 977 (85.0%) were returned, comparable to the original survey response in 2008 (757 of 907; 83.5%). New participants submitted 124 of 977 (12.7%) surveys. The median laboratory accession rate was 14 788 cases with 211 HER2 tests performed annually. Testing was validated with fluorescence in situ hybridization in 49.1% (443 of 902) of the laboratories; 26.3% (224 of 853) of the laboratories used another IHC assay. The median number of cases to validate fluorescence in situ hybridization (n = 40) and IHC (n = 27) was similar to those in 2008. Ninety-five percent concordance with fluorescence in situ hybridization was achieved by 76.5% (254 of 332) of laboratories for IHC− findings and 70.4% (233 of 331) for IHC+ cases. Ninety-five percent concordance with another IHC assay was achieved by 71.1% (118 of 168) of the laboratories for negative findings and 69.6% (112 of 161) of the laboratories for positive cases. The proportion of laboratories interpreting HER2 IHC using ASCO/CAP guidelines (86.6% [798 of 921] in 2011; 83.8% [605 of 722] in 2008) remains similar. Conclusions.—Although fixation time improvements have been made, assay validation deficiencies still exist. The results of this survey were shared within the CAP, including the Laboratory Accreditation Program and the ASCO/CAP panel revising the HER2 guidelines published in October 2013. The Laboratory Accreditation Program checklist was changed to strengthen HER2 validation practices.

scholarly journals Impact of the 2018 American Society of Clinical Oncology/College of American Pathologists HER2 Guideline Updates on HER2 Assessment in Breast Cancer With Equivocal HER2 Immunohistochemistry Results With Focus on Cases With HER2/CEP17 Ratio <2.0 and Average HER2 Copy Number ≥4.0 and <6.0

2019 ◽  
Vol 144 (5) ◽  
pp. 597-601 ◽  
Author(s):  
Raza S. Hoda ◽  
Edi Brogi ◽  
Jin Xu ◽  
Katia Ventura ◽  
Dara S. Ross ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Clinical Oncology ◽  
Copy Number ◽  
Her2 Overexpression ◽  
Breast Cancers ◽  
American Society ◽  
Dual Probe

Context.— The American Society of Clinical Oncology/College of American Pathologists HER2 testing guideline in breast cancer was updated in 2018 to address issues on interpretation of uncommon results using dual-probe in situ hybridization according to the 2013 guideline. Objective.— To assess impact of the 2018 guideline on breast cancer with equivocal HER2 immunohistochemistry results. Design.— We retrospectively reviewed HER2 fluorescence in situ hybridization (FISH) data (HER2/CEP17 ratio and average HER2 copy number per cell) of HER2 immunohistochemistry–equivocal (2+ or 1+ to 2+) breast cancers at our center between January 2014 and May 2018 and compared HER2 FISH results according to 2013 and 2018 guidelines. Results.— A total of 1666 HER2 FISH results from 1421 patients with equivocal HER2 immunohistochemistry were reviewed. Based on the 2013 guideline, HER2 FISH results were amplified in 346 cases (20.8%), equivocal in 242 (14.5%), and nonamplified in 1078 (64.7%). Using the 2018 guideline, 258 cases (16%) were reclassified, including 242 previously equivocal test results (15%) and 16 previously positive results (1%) reclassified as negative. The subset of 2013 HER2-equivocal and 2018 HER2-nonamplified cases with HER2/CEP17 ratio lower than 2.0 and average HER2 copy number 4.0 or higher and lower than 6.0 showed higher incidence of micropapillary morphology compared with HER2-amplified cases. Despite most patients in this group not receiving HER2-targeted treatment, 96% had no evidence of disease at follow-up. Conclusions.— The 2018 guideline eliminated HER2 FISH–equivocal cases by reclassifying HER2-equivocal cases and cases with nonclassical amplification without HER2 overexpression as HER2 negative. As a consequence, we observed a considerable increase in HER2 FISH–negative cases and a slight decrease in HER2 FISH–positive cases.

American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer

2007 ◽  
Vol 131 (1) ◽  
pp. 18-43 ◽  
Author(s):  
Antonio C. Wolff ◽  
M. Elizabeth H. Hammond ◽  
Jared N. Schwartz ◽  
Karen L. Hagerty ◽  
D. Craig Allred ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
In Situ Hybridization ◽  
Growth Factor Receptor ◽  
Her2 Gene ◽  
Her2 Testing ◽  
Gene Copies ◽  
Epidermal Growth ◽  
American Society

Abstract Purpose.—To develop a guideline to improve the accuracy of human epidermal growth factor receptor 2 (HER2) testing in invasive breast cancer and its utility as a predictive marker. Methods.—The American Society of Clinical Oncology and the College of American Pathologists (CAP) convened an expert panel, which conducted a systematic review of the literature and developed recommendations for optimal HER2 testing performance. The guideline was reviewed by selected experts and approved by the board of directors for both organizations. Results.—Approximately 20% of current HER2 testing may be inaccurate. When carefully validated testing is performed, available data do not clearly demonstrate the superiority of either immunohistochemistry (IHC) or in situ hybridization (ISH) as a predictor of benefit from anti-HER2 therapy. Recommendations.—The panel recommends that HER2 status should be determined for all invasive breast cancer. A testing algorithm that relies on accurate, reproducible assay performance, including newly available types of brightfield ISH, is proposed. Elements to reliably reduce assay variation (for example, specimen handling, assay exclusion, and reporting criteria) are specified. An algorithm defining positive, equivocal, and negative values for both HER2 protein expression and gene amplification is recommended: a positive HER2 result is IHC staining of 3+ (uniform, intense membrane staining of &gt; 30% of invasive tumor cells), a fluorescent in situ hybridization (FISH) result of more than 6 HER2 gene copies per nucleus, or a FISH ratio (HER2 gene signals to chromosome 17 signals) of more than 2.2; a negative result is an IHC staining of 0 or 1+, a FISH result of less than 4.0 HER2 gene copies per nucleus, or a FISH ratio of less than 1.8. Equivocal results require additional action for final determination. It is recommended that to perform HER2 testing, laboratories show 95% concordance with another validated test for positive and negative assay values. The panel strongly recommends validation of laboratory assay or modifications, use of standardized operating procedures, and compliance with new testing criteria to be monitored with the use of stringent laboratory accreditation standards, proficiency testing, and competency assessment. The panel recommends that HER2 testing be done in a CAP-accredited laboratory or in a laboratory that meets the accreditation and proficiency testing requirements set out by this document.

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