HER2/neu revisited: quality and interpretive issues

Ahmed, Syed Salahuddin; Iqbal, Jabed; Thike, Aye Aye; Lim, Alvin Soon Tiong; Lim, Tse Hui; Tien, Sim Leng; Tan, Puay Hoon

doi:10.1136/jcp.2010.085423

Cited by 12 publications

(9 citation statements)

References 63 publications

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“…Areas such as ductal carcinoma in situ and necrotic, sclerotic, and hemorrhagic areas should be avoided, and FISH testing should only be carried out on the delineated invasive tumor areas. 32 On the other hand, IHC/FISH discrepancies, especially false-positive IHC results, were thought likely to be due to an interpretive error rather than a technical error. 16 Concurring with this observation, the positive concordance in our study was noted to be slightly lower than the negative concordance.…”

Section: Resultsmentioning

confidence: 99%

Implications of the Updated 2013 American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations on Human Epidermal Growth Factor Receptor 2 Gene Testing Using Immunohistochemistry and Fluorescence In Situ Hybridization for Breast Cancer

Lim

Lim²,

Thike³

et al. 2016

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Human epidermal growth factor receptor 2 (HER2/neu) amplification is used as a predictive marker for trastuzumab treatment in breast cancer. Objective.-To assess the impact of the revised ASCO/ CAP recommendations on both IHC and FISH results by using the dual-color HER2/neu and centromeric FISH probes.Design.-Retrospective analysis of 590 invasive carcinomas with concurrent IHC and dual-color HER2/neu and centromeric 17 (CEP17) FISH results, based on 2007 ASCO/CAP guidelines, was conducted from July 2011 to June 2013. With the revised guidelines, patients were recategorized and concordance rates between the 2 assays were recalculated.Results.-Overall concordance rates for FISH and IHC decreased from 94.9% to 93.8% with reclassification. Negative FISH cases decreased from 79.1% to 69.3%. However, equivocal FISH cases were significantly increased from 0.7% to 9.5%, leading to more retesting. Both positive IHC and FISH cases were also noted to be increased, leading to more patients being eligible for trastuzumab treatment, especially those patients with concurrent HER2/neu and CEP17 polysomy. Approximately 1% of patients with initial FISH negative results were reclassified as having positive results when both the ratios and average copy number of HER2/neu were considered under the revised guidelines.Conclusions.-The revised 2013 ASCO/CAP guidelines can potentially lead to more patients being eligible for trastuzumab therapy but additional retesting is to be expected owing to an increased number of equivocal FISH cases.

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Section: Resultsmentioning

confidence: 99%

Implications of the Updated 2013 American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations on Human Epidermal Growth Factor Receptor 2 Gene Testing Using Immunohistochemistry and Fluorescence In Situ Hybridization for Breast Cancer

Lim

Lim²,

Thike³

et al. 2016

Archives of Pathology &Amp; Laboratory Medicine

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“…An accompanying explanation/interpretation of the HER2 status from the pathologist(s) is critical to help guide the clinician in making appropriate management decisions [4]. The patient also needs to be informed of challenges associated with HER2 testing, particularly in cases near the FISH ratio of 2.0 as recommended by the FDA.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemistry and fluorescence in situ hybridization assessment of HER2 in clinical trials of adjuvant therapy for breast cancer (NCCTG N9831, BCIRG 006, and BCIRG 005)

Perez

Press

Dueck

et al. 2013

Breast Cancer Res Treat

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A comprehensive, blinded, pathology evaluation of HER2 testing in HER2-positive/negative breast cancers was performed among three central laboratories. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analyses were performed on 389 tumor blocks from three large adjuvant trials: N9831, BCIRG-006, and BCIRG-005. In 123 cases, multiple blocks were examined. HER2 status was defined according to FDA-approved guidelines and was independently re-assessed at each site. Discordant cases were adjudicated at an on-site, face-to-face meeting. Results across three independent pathologists were concordant by IHC in 351/381 (92 %) and FISH in 343/373 (92 %) blocks. Upon adjudication, consensus was reached on 16/30 and 18/30 of discordant IHC and FISH cases, respectively, resulting in overall concordance rates of 96 and 97 %. Among 155 HER2-negative blocks, HER2 status was confirmed in 153 (99 %). In the subset of 102 HER2-positive patients from N9831/BCIRG-006, primary blocks from discordant cases were selected, especially those with discordant test between local and central laboratories. HER2 status was confirmed in 73 (72 %) of these cases. Among 118 and 113 cases with IHC and FISH results and >1 block evaluable, block-to-block variability/heterogeneity in HER2 results was seen in 10 and 5 %, respectively. IHC−/FISH− was confirmed for 57/59 (97 %) primary blocks from N9831 (locally positive, but centrally negative); however, 5/22 (23 %) secondary blocks showed HER2 positivity. Among 53 N9831 patients with HER2-normal disease adjudicated as IHC−/FISH—(although locally positive), there was a non-statistically significant improvement in disease-free survival with concurrent trastuzumab compared to chemotherapy alone (adjusted hazard ratio 0.34; 95 % CI, 0.11–1.05; p = 0.06). There were similar agreements for IHC and FISH among pathologists (92 % each). Agreement was improved at adjudication (96 %). HER2 tumor heterogeneity appears to partially explain discordant results in cases initially tested as positive and subsequently called negative.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-013-2444-y) contains supplementary material, which is available to authorized users.

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“…Several publications have demonstrated a very good concordance between the results obtained by IHC and FISH for the determination of HER2 status in breast cancer specimens (8,9). Other studies, however, have reported up to 13% of FISH-positive cases among those scoring negative by IHC (10)(11)(12)(13)(14)(15).…”

mentioning

confidence: 87%

Concordance of HER2 Immunohistochemistry and Fluorescence In Situ Hybridization Using Tissue Microarray in Breast Cancer

Furrer

Jacob

Caron

et al. 2017

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HER2/neu revisited: quality and interpretive issues

Abstract: Concordance between IHC and FISH assay was excellent and within the published range (104/106=98.1%). The discordant cases represent a well-recognised subset of genetic heterogeneity in HER2/neu, which is known to contribute to positive IHC and negative FISH tests.

Cited by 12 publications

References 63 publications

Implications of the Updated 2013 American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations on Human Epidermal Growth Factor Receptor 2 Gene Testing Using Immunohistochemistry and Fluorescence In Situ Hybridization for Breast Cancer

Implications of the Updated 2013 American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations on Human Epidermal Growth Factor Receptor 2 Gene Testing Using Immunohistochemistry and Fluorescence In Situ Hybridization for Breast Cancer

Immunohistochemistry and fluorescence in situ hybridization assessment of HER2 in clinical trials of adjuvant therapy for breast cancer (NCCTG N9831, BCIRG 006, and BCIRG 005)

Concordance of HER2 Immunohistochemistry and Fluorescence In Situ Hybridization Using Tissue Microarray in Breast Cancer

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