Well‐differentiated invasive breast cancers with equivocal <scp>HER</scp>2 immunohistochemistry: what is the yield of routine reflex <i>in‐situ</i> hybridization testing?

Bethune, Gillian C.; Pettit, Alexandra S L; Zanten, Daniel Veldhuijzen van; Barnes, Penelope J

doi:10.1111/his.13160

Cited by 11 publications

(15 citation statements)

References 33 publications

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“…Commonly used tests include immunohistochemistry (IHC), [92] fluorescence in situ hybridization (FISH), [93] or comparative genomic hybridization (CGH). [94] IHC exploits the principle of antibodies conjugated with enzymes for the specific binding to the antigens in biological tissues.…”

Section: Melanoma Diagnosis and Detection Methodsmentioning

confidence: 99%

Soft Probes for Bio-electrochemical Imaging

Lin

2019

Springer Theses

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Section: Melanoma Diagnosis and Detection Methodsmentioning

confidence: 99%

Soft Probes for Bio-electrochemical Imaging

Lin

2019

Springer Theses

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“…The activation of the mitogen-activated protein kinase (MAPK) and the phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt) pathways due to HER2 homo- or hetero-dimerisation promotes tumour cell proliferation, differentiation, survival and migration, causing adverse pathological disease and poor prognosis [ 27 , 32 , 33 ]. Biological responses of the activated signalling pathways are precisely dependent on the ligands involved and dimers formed; thus, dysregulation of HER receptors can result in aberrant signalling, leading to fundamental biological processes to be altered [ 34 , 35 , 36 ]. Moreover, cell polarity and adhesion are specifically disrupted by HER2 activation, which can cause aberrant asymmetric cell division and subsequent overgrowth of less differentiated cells [ 37 , 38 ].…”

Section: Her2 Breast Cancermentioning

confidence: 99%

“…This process occurs through the binding of the Par6 and atypical protein kinase C (Par6-aPKC) components of the Par complex upon HER2 activation [ 37 ]. Thus, HER2(+) tumours are poorly differentiated [ 36 , 39 ]. Amplification of the HER2 gene, located on chromosome 17 (17q12q21), leads to the overexpression of HER2 receptors and is highly associated with increased cell proliferation, tumorigenesis and invasion, resulting in distant metastases [ 33 , 40 ].…”

Section: Her2 Breast Cancermentioning

confidence: 99%

Diagnostics and Therapeutics in Targeting HER2 Breast Cancer: A Novel Approach

Mandarano

Shigdar

2021

IJMS

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Breast cancer is one of the most commonly occurring cancers in women globally and is the primary cause of cancer mortality in females. BC is highly heterogeneous with various phenotypic expressions. The overexpression of HER2 is responsible for 15–30% of all invasive BC and is strongly associated with malignant behaviours, poor prognosis and decline in overall survival. Molecular imaging offers advantages over conventional imaging modalities, as it provides more sensitive and specific detection of tumours, as these techniques measure the biological and physiological processes at the cellular level to visualise the disease. Early detection and diagnosis of BC is crucial to improving clinical outcomes and prognosis. While HER2-specific antibodies and nanobodies may improve the sensitivity and specificity of molecular imaging, the radioisotope conjugation process may interfere with and may compromise their binding functionalities. Aptamers are single-stranded oligonucleotides capable of targeting biomarkers with remarkable binding specificity and affinity. Aptamers can be functionalised with radioisotopes without compromising target specificity. The attachment of different radioisotopes can determine the aptamer’s functionality in the treatment of HER2(+) BC. Several HER2 aptamers and investigations of them have been described and evaluated in this paper. We also provide recommendations for future studies with HER2 aptamers to target HER2(+) BC.

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“…HER2/neu amplification has been associated with a poor prognosis due to the activation of the growthsignaling pathway that leads to tumor cell proliferation. Trastuzumab and other anti-HER2/neu therapies have been proven to be an effective treatment for HER2/neu positive breast cancer patients [3]. Screening programmes for HER2/ neu expression in breast carcinoma patients has also been proven to reduce the cost of therapy [4].…”

Section: Introductionmentioning

confidence: 99%

“…A study on the impact of these modified cut-offs revealed a 2% increase in overall HER2/neupositivity at their institution [5]. Current guidelines recommend testing for HER2/neuamplification for all invasive breast cancers with fluorescence in situ hybridization that are equivocal on immunohistochemical analysis [3].…”

Section: Introductionmentioning

confidence: 99%

HER2/neu status detection in breast carcinoma: Is FISH the preferred approach over IHC

Harit¹,

K²,

Udupa³

et al. 2019

Trop J Pathol Microbiol

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Background: HER2/neu amplification is found in 15-30% of all breast cancer patients, which can be detected by either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). The concordance of FISH and IHC analysis for HER2/neu amplification remains limited, especially with studies in the Indian population. There is a need to further classify this information as HER2/neu positive patients often have a worse disease prognosis and require anti-HER2/neu therapy. Methods: In a retrospective study 149 patients with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC), who underwent both IHC and FISH testing for HER2/neu amplification were analysed to determine the concordance between the two tests in this population. Results: Out of 149 patients reviewed, 58 had equivocal results on IHC, 52 patients had negative results and 39 patients had positive results on IHC. Analysis of the 91 non-equivocal IHC cases and their FISH results demonstrated an inter-rater reliability of Kappa= 0.606 (p <0.0005) 95% CI (0.445, 0.767). Of the 52 patients with negative IHC scores, 13 (25%) were found to be positive on FISH testing for HER/neu amplification. This represents a substantial number of patients who otherwise would not have received anti-HER2/neu therapy. Conclusions: The present results indicate that FISH testing for HER2/neu status should be done on all breast cancer patients whenever possible, irrespective of IHC score status so that appropriate treatment decisions can be made. The higher sensitivity and specificity of FISH testing can reduce the number of both false positive and false negatives seen with immunohistochemistry testing in the present study.

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Well‐differentiated invasive breast cancers with equivocal HER2 immunohistochemistry: what is the yield of routine reflex in‐situ hybridization testing?

Abstract: The rate of HER2 amplification among well-differentiated breast cancers is very low. Basolateral staining in well-differentiated tumours may be overinterpreted as HER2 IHC 2+, but is rarely associated with HER2 amplification.

Cited by 11 publications

References 33 publications

Soft Probes for Bio-electrochemical Imaging

Soft Probes for Bio-electrochemical Imaging

Diagnostics and Therapeutics in Targeting HER2 Breast Cancer: A Novel Approach

HER2/neu status detection in breast carcinoma: Is FISH the preferred approach over IHC

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