False positivity in HER2 testing of breast cancer: novel paths for approaching an old dilemma

Nunes, Cristiana Buzelin; Buzelin, Marcelo Araújo; Balabram, Débora; Foureaux, Fernanda de Souza; Porto, Simone; Gobbi, Helenice

doi:10.1136/jclinpath-2013-201647

Cited by 10 publications

(9 citation statements)

References 30 publications

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“…A key consideration for proper molecular diagnosis of cancers is to account for inter‐ and intratumor heterogeneity. Issues with correctly diagnosing oncogene alterations from patient to patient could be influenced by the particular test used, as has been noted for expression‐based tests for HER2 amplification —diagnostics focused on the specific detection of somatic cancer mutations will likely prove superior. Tumor biopsies can be biased by analyses of a small portion of the tumor that does not appropriately reflect intratumor heterogeneity, as has been documented in glioblastoma , or that does not capture the mutational heterogeneity of disseminated disease .…”

Section: A Road Map For Targeting Oncogene Addictionmentioning

confidence: 99%

Oncogene addiction: pathways of therapeutic response, resistance, and road maps toward a cure

2015

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A key goal of cancer therapeutics is to selectively target the genetic lesions that initiate and maintain cancer cell proliferation and survival. While most cancers harbor multiple oncogenic mutations, a wealth of preclinical and clinical data supports that many cancers are sensitive to inhibition of single oncogenes, a concept referred to as 'oncogene addiction'. Herein, we describe the clinical evidence supporting oncogene addiction and discuss common mechanistic themes emerging from the response and acquired resistance to oncogene-targeted therapies. Finally, we suggest several opportunities toward exploiting oncogene addiction to achieve curative cancer therapies.

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Section: A Road Map For Targeting Oncogene Addictionmentioning

confidence: 99%

Oncogene addiction: pathways of therapeutic response, resistance, and road maps toward a cure

2015

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“…However, both HER2 IHC and HER2 ISH assays have their own advantages and disadvantages in achieving optimum test results. 15,16 and signal detection systems. Furthermore, due to the lack of internal control within a tissue section, there is a reasonable concern with the reliability of HER2 IHC assays, especially when HER2 IHC results are negative.…”

Section: Her2 Status Assessment Of Breast Cancer Patientsmentioning

confidence: 99%

“…HER2 IHC equivocal cases must be reexamined with a different tissue block, if available, or by HER2 ISH assay. The specificity and sensitivity of HER2 IHC assays are influenced by selections of pretreatment conditions, antibody clones, and signal detection systems. Furthermore, due to the lack of internal control within a tissue section, there is a reasonable concern with the reliability of HER2 IHC assays, especially when HER2 IHC results are negative.…”

Section: Introductionmentioning

confidence: 99%

The assessment of HER2 status in breast cancer: the past, the present, and the future

Nitta

Kelly

Allred

et al. 2016

Pathology International

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Humanized monoclonal anti-human growth factor receptor 2 (HER2) antibody trastuzumab was approved for HER2 positive breast cancer patient treatment 11 years after the demonstration of HER2 gene amplification associated with the HER2 protein overexpression in breast cancer in 1987. HER2 positive status of breast cancer patients is assessed by HER2 gene amplification with in situ hybridization (ISH) and/or HER2 protein overexpression with immunohistochemistry (IHC). Because the discordance between quantitative HER2 ISH and subjective, semiquantitative HER2 IHC assay results is a well-recognized issue of HER2 testing, we developed an assay combining HER2 ISH and HER2 IHC assays (HER2 gene-protein assay; HER2 GPA) as one test on the same tissue section. HER2 GPA allows pathologists to score the HER2 gene and HER2 protein status simultaneously at the individual cell level. The possibility that HER2 GPA may become the next generation of HER2 testing is discussed, particularly for cases in which it is difficult to assess the HER2 status of breast cancer patients due to the HER2 heterogeneity.

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“…The analytic sensitivity difference is not corroborated by several previously published reports comparing 4B5 and HercepTest. [26][27][28] Prior comparative studies of HER2 immunostains using patient tissue samples evaluated concordance to each other and to fluorescence in situ hybridization amplification data.…”

mentioning

confidence: 99%

Quantitative Assessment of Immunohistochemistry Laboratory Performance by Measuring Analytic Response Curves and Limits of Detection

Sompuram¹,

Vani²,

Schaedle³

et al. 2018

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Numerous studies highlight interlaboratory performance variability in diagnostic immunohistochemistry (IHC) testing. Despite substantial improvements over the years, the inability to quantitatively and objectively assess immunostain sensitivity complicates interlaboratory standardization.Objective.-To quantitatively and objectively assess the sensitivity of the immunohistochemical stains for human epidermal growth factor receptor type 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) across IHC laboratories in a proficiency testing format. We measure sensitivity with parameters that are new to the field of diagnostic IHC: analytic response curves and limits of detection.Design.-Thirty-nine diagnostic IHC laboratories stained a set of 3 slides, one each for HER2, ER, and PR. Each slide incorporated a positive tissue section and IHControls at 5 different concentrations. The IHControls comprise cell-sized clear microbeads coated with defined concentrations of analyte (HER2, ER, and/or PR). The laboratories identified the limits of detection and then mailed the slides for quantitative assessment.Results.-Each commercial immunostain demonstrated a characteristic analytic response curve, reflecting strong reproducibility among IHC laboratories using the same automation and reagents prepared per current Good Manufacturing Practices. However, when comparing different commercial vendors (using different reagents), the data reveal up to 100-fold differences in analytic sensitivity. For proficiency testing purposes, quantitative assessment using analytic response curves was superior to subjective interpretation of limits of detection.Conclusions.-Assessment of IHC laboratory performance by quantitative measurement of analytic response curves is a powerful, objective tool for identifying outlier IHC laboratories. It uniquely evaluates immunostain performance across a range of defined analyte concentrations.

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False positivity in HER2 testing of breast cancer: novel paths for approaching an old dilemma

Abstract: There was very good agreement among the five anti-HER2 antibodies. CB11 was the most specific antibody, but showed more false negative cases. A0485, SP3, 4B5 and HercepTest were highly sensitive and specific, but showed more false positive cases.

Cited by 10 publications

References 30 publications

Oncogene addiction: pathways of therapeutic response, resistance, and road maps toward a cure

Oncogene addiction: pathways of therapeutic response, resistance, and road maps toward a cure

The assessment of HER2 status in breast cancer: the past, the present, and the future

Quantitative Assessment of Immunohistochemistry Laboratory Performance by Measuring Analytic Response Curves and Limits of Detection

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