Standardization of HER2 Immunohistochemistry in Breast Cancer by Automated Quantitative Analysis

2009 ◽  
Vol 133 (9) ◽  
pp. 1413-1419 ◽  
Author(s):  
Mark D. Gustavson ◽  
Brian Bourke-Martin ◽  
Dylan Reilly ◽  
Melissa Cregger ◽  
Christine Williams ◽  
...  
Keyword(s):  
Quantitative Analysis ◽  
Clinical Oncology ◽  
Clinical Laboratory ◽  
Breast Cancers ◽  
Her2 Testing ◽  
Coefficients Of Variation ◽  
American Society ◽  
New Guidelines ◽  
Calibration Techniques ◽  
New Generation

Abstract Context.—There is critical need for standardization of HER2 immunohistochemistry testing in the clinical laboratory setting. Recently, the American Society of Clinical Oncology and the College of American Pathologists have submitted guidelines recommending that laboratories achieve 95% concordance between assays and observers for HER2 testing. Objective.—As a potential aid to pathologists for achieving these new guidelines, we have conducted an examination using automated quantitative analysis (AQUA analysis) to provide a standardized HER2 immunohistochemistry expression score across instruments (sites), operators, and staining runs. Design.—We analyzed HER2 expression by immunohistochemistry in a cohort (n = 669) of invasive breast cancers in tissue microarray format across different instruments (n = 3), operators (n = 3), and staining runs (n = 3). Using light source, instrument calibration techniques, and a new generation of image analysis software, we produced normalized AQUA scores for each parameter and examined their reproducibility. Results.—The average percent coefficients of variation across instruments, operators, and staining runs were 1.8%, 2.0%, and 5.1%, respectively. For positive/negative classification between parameters, concordance rates ranged from 94.5% to 99.3% for all cases. Differentially classified cases only occurred around the determined cut point, not over the entire distribution. Conclusions.—These data demonstrate that AQUA analysis can provide a standardized HER2 immunohistochemistry test that can meet current guidelines by the American Society of Clinical Oncology/College of American Pathologists. The use of AQUA analysis could allow for standardized and objective HER2 testing in clinical laboratories.

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.

American Society of Clinical Oncology/College of American Pathologists 2018 Focused Update of Breast Cancer HER2 FISH Testing GuidelinesResults From a National Reference Laboratory

2019 ◽  
Vol 152 (4) ◽  
pp. 479-485 ◽  
Author(s):  
Leo Lin ◽  
Deepika Sirohi ◽  
Joshua F Coleman ◽  
H Evin Gulbahce
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast ◽  
Reference Laboratory ◽  
National Reference Laboratory ◽  
Breast Cancers ◽  
National Reference ◽  
American Society ◽  
New Guidelines ◽  
Her2 Positivity

Abstract Objectives To review impact of the ASCO/CAP 2018 update on HER2 testing. Methods HER2 fluorescence in situ hybridization (FISH) test requests from primary and metastatic breast cancers between August 2018 and January 2019 were included. FISH results requiring a changed algorithm under the new guidelines (groups 2, 3, and 4) were identified and HER2:CEN17 ratios, average HER2, CEN17 signals/cell, and HER2 immunohistochemistry (IHC) results were recorded. Results Of the HER2 FISH cases 176/812(21.7%) fell within groups 2, 3, or 4; 0/12, 1/12, and 2/152 cases were positive (3+) by IHC, and 1/12, 2/12, and 6/152 cases were positive after targeted scoring from groups 2, 3, and 4, respectively. Following 2018 updates, 8.3%, 25%, and 5.3% of the groups 2, 3, and 4 were positive, respectively. Conclusions Groups 2, 3, and 4 constituted over 20% of HER2 FISH tests in a reference laboratory. The 2018 ASCO/CAP update significantly decreased the HER2 positivity rate.

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.

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.

scholarly journals Impact of the 2018 ASCO/CAP guidelines on HER2 fluorescence in situ hybridization interpretation in invasive breast cancers with immunohistochemically equivocal results

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Bo Wang ◽  
Wei Ding ◽  
Ke Sun ◽  
Xiaoling Wang ◽  
Liming Xu ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Group 2 ◽  
Gene Status ◽  
American Society ◽  
New Guidelines ◽  
The Impact

Abstract The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) recently issued updated guidelines on human epidermal growth factor receptor 2 (HER2) testing by fluorescence in situ hybridization (FISH) in invasive breast cancers. In this study, we aimed to investigate the impact of the new recommendations on HER2 FISH interpretation in invasive breast cancers with immunohistochemically (IHC) equivocal results. 1810 breast cancer cases with IHC equivocal results were enrolled in this study between January 2012 and May 2019. Concomitant IHC was performed on the same tissue blocks detected by FISH testing. According to the 2018 guidelines, all the cases in ISH group 2 were categorized as HER2 negative; three of four cases in ISH group 3 were considered as HER2 positive, while the one scored IHC 1+ was reclassified as HER2 negative; Fifty-three previously ISH equivocal cases were redistributed into ten HER2-positive cases and forty-three HER2-negative cases. In conclusion, the utility of 2018 ASCO/CAP guidelines resulted in a slight decrease in HER2 positive rate, due to the reclassification of cases in ISH group 2 and group 4. The implementation of the new guidelines can reduce reflex FISH test and make the diagnosis of HER2 gene status more definitive.

American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer (Unabridged Version)

2010 ◽  
Vol 134 (7) ◽  
pp. e48-e72 ◽  
Author(s):  
M. Elizabeth H. Hammond ◽  
Daniel F. Hayes ◽  
Mitch Dowsett ◽  
D. Craig Allred ◽  
Karen L. Hagerty ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Oncology ◽  
Randomized Clinical Trials ◽  
False Negative ◽  
Progesterone Receptors ◽  
Breast Cancers ◽  
Interpretation Criteria ◽  
Assay Performance ◽  
American Society ◽  
Testing Algorithm

Abstract Purpose.—To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers. Methods.—The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance. Results.—Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate (false negative or false positive). Most of the issues with testing have occurred because of variation in pre-analytic variables, thresholds for positivity, and interpretation criteria. Recommendations.—The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, reproducible assay performance is proposed. Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials.

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