Impact of an alternative chromosome 17 probe and the 2013 American Society of Clinical Oncology and College of American Pathologists guidelines on fluorescence in situ hybridization for the determination of <i>HER2</i> gene amplification in breast cancer

Donaldson, Alana R.; Shetty, Shashirekha; Wang, Zhen; Rivera, Christine; Portier, Bryce P.; Budd, G. Thomas; Downs‐Kelly, Erinn; Lanigan, Christopher; Calhoun, Benjamin C.

doi:10.1002/cncr.30592

Cited by 28 publications

(30 citation statements)

References 41 publications

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“…6 Alternate chromosome 17 reference probes may aid in establishing the true HER2 status. [6][7][8][9] Unfortunately, the current guidelines do not offer a definite recommendation for the specific use of the probes, nor do they provide guidance for which particular probe to use. Here we describe our institutional experience using D17S122 for reflex FISH testing on double-equivocal invasive breast carcinomas and review the literature on double-equivocal HER2 cases with a focus on FISH evaluation using alternate reference probes for determining HER2 status.…”

Section: 2mentioning

confidence: 99%

“…A number of studies [6][7][8][9]27 used alternate reference probes for chromosome 17 in an attempt to clarify the true status of HER2 and chromosome 17 in breast carcinomas and the comparative utility of the CEP17 probe. Genomic studies 28,29 have shown chromosome 17 polysomy to be a rare event in breast carcinomas.…”

Section: Fish For Her2 Using Alternate Reference Probesmentioning

confidence: 99%

“…9 Intuitively, ratios comparing HER2:D17S122 would thus be accurate in determining genuine HER2 status. Mansfield 7 performed an analysis using D17S122 on primary and metastatic breast carcinomas. All of their cases had copy number alteration of CEP17 as defined by an average copy number below 1.5 and 2.6 or greater.…”

Section: Fish For Her2 Using Alternate Reference Probesmentioning

confidence: 99%

“…Interestingly, none of the patients showed disease recurrence or progression at follow-up (3-46 months), including those who did not receive anti-HER2 therapy. 7 More recently, Holzschuh et al 27 analyzed samples with (82) and without (52) increased centromere 17 (cen17) copy numbers and 78 evidently HER2 amplified cases using dual-(HER2/CEP17 and ERBB2/D17S122) and triple-marker hybridization probes (HER2/cen17/TP53 and HER2/cen17/ RAI1). In addition, the investigators subjected selected putative polysomic samples (.2 copies of cen17) to arraybased comparative genomic hybridization (aCGH).…”

Section: Fish For Her2 Using Alternate Reference Probesmentioning

confidence: 99%

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Double-Equivocal HER2 Invasive Breast Carcinomas: Institutional Experience and Review of Literature

Griffin

Pincus

Siziopikou

et al. 2018

Archives of Pathology &Amp; Laboratory Medicine

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Context.— HER2 status is a prognostic factor and therapeutic target in invasive breast carcinomas. Reflex testing using an alternate method is recommended on equivocal cases via immunohistochemistry or fluorescence in situ hybridization (FISH). Therapeutic dilemmas arise when both tests are equivocal. The standard chromosome 17 centromere reference probe (CEP17) is in close proximity to the HER2 locus and may be coamplified, leading to equivocal results. Alternate chromosome 17 reference probes may aid in establishing the true HER2 status. Objective.— To describe our institutional experience using D17S122 probe for reflex FISH testing on double-equivocal invasive breast carcinomas and review the literature on alternate reference probes. Data Sources.— Twenty-two patients with double-equivocal invasive breast carcinomas, defined as HER2 immunohistochemistry score 2+ and FISH equivocal per the 2013 guidelines, were reviewed. Reflex FISH was performed with alternate probe D17S122 and the HER2 status classified for 11 cases by using a revised HER2:D17S122 ratio. Seven of 11 cases (63.6%) were ultimately classified as HER2 positive, while 4 cases (36.4%) remained equivocal. The 7 positive cases showed a HER2:D17S122 greater than 2.0. Conclusions.— Alternate probe D17S122 reclassified more than half of our cases as HER2 positive. Alternate probes may establish true HER2 status and direct proper management, as evidenced by our experience and the literature. Additional investigation is needed to determine which alternate probe(s) is(are) best for reflex testing. Finally, the American Society of Clinical Oncology/College of American Pathologists guidelines may need to be updated to reflect more specific recommendations for the utilization of appropriate probes in double-equivocal HER2 cases.

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Section: 2mentioning

confidence: 99%

Section: Fish For Her2 Using Alternate Reference Probesmentioning

confidence: 99%

Section: Fish For Her2 Using Alternate Reference Probesmentioning

confidence: 99%

Section: Fish For Her2 Using Alternate Reference Probesmentioning

confidence: 99%

See 2 more Smart Citations

Double-Equivocal HER2 Invasive Breast Carcinomas: Institutional Experience and Review of Literature

Griffin

Pincus

Siziopikou

et al. 2018

Archives of Pathology &Amp; Laboratory Medicine

View full text Add to dashboard Cite

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“…The most commonly used FISH assay is the dual-probe assay, 1 fluorescently labeled probe hybridizing to the target HER2 gene, and 1 probe hybridizing to the centromeric region of chromosome 17 on which the HER2 gene is located. 5 The latter probe, CEP17, is used as a surrogate marker for the chromosome 17 number, and thus increased CEP17 signals above a certain threshold are considered to indicate the presence of polysomy 17. 6 However, recent studies with broader genomic approaches, including comparative genomic hybridization and multiplex ligation-dependent probe amplification, have demonstrated the rarity of true polysomy in breast cancers, and increased CEP17 signals were thought to be due to the pericentromeric amplifications.…”

mentioning

confidence: 99%

Utility of Alternate, Noncentromeric Chromosome 17 Reference Probe for Human Epidermal Growth Factor Receptor Fluorescence In Situ Hybridization Testing in Breast Cancer Cases

Pai

Shet

Patil

et al. 2018

Archives of Pathology &Amp; Laboratory Medicine

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Context PathVysion-a US Food and Drug Administration-approved dual-probe human epidermal growth factor receptor ( HER2) fluorescence in situ hybridization (FISH) assay-provides the HER2: CEP17 ratio, a centromeric enumeration probe ratio for determining HER2 status in breast cancers. However, pericentromeric amplifications might then skew the HER2: CEP17 ratio, underestimating the HER2 status, which calls into question the use of CEP17 as the reference probe. Objective To analyze the utility of a noncentromeric chromosome 17 reference locus ( D17S122) to assess HER2 gene status in cases showing "nonclassical" FISH patterns with the CEP17 probe. Design The HER2 status of breast cancers accessioned in the years 2015-2017, displaying "nonclassical" or "equivocal" results by the PathVysion (Abbott Molecular Inc, Des Plaines, Illinois) HER2 DNA Probe Kit were reflex tested using an alternate FISH probe (ZytoLight SPEC/D17S122, ZytoVision, Bremerhaven, Germany) and interpreted with American Society of Clinical Oncology/College of American Pathologists 2013 guidelines. Results Of 37 cases, 17 were FISH equivocal. With the alternate D17S122 probe, 13 (76.4%) were reclassified as amplified, 3 (17.6%) as nonamplified, and a single case retained an equivocal result. Of the 17 cases with a chromosome 17 polysomy pattern, disomy, polysomy, and monosomy patterns were seen with 14 cases, 2 cases, and 1 case, respectively. Within the 17 cases with polysomy pattern, 3 (17.6%) demonstrated an unusual colocalization pattern of HER2 and CEP17, which was not observed with the alternate probe. Conclusions The denominator-stable alternate probe is a useful adjunct in the diagnostic armamentarium to analyze HER2 status in cases with FISH equivocal and complex patterns.

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Assessment ofERBB2/HER2Status inHER2-Equivocal Breast Cancers by FISH and 2013/2014 ASCO-CAP Guidelines

et al. 2019

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Key Points Questions How does one assess the status of HER2 ISH-equivocal breast cancers as either HER2 positive or HER2 negative for treatment purposes, and are the use of alternative controls, as recommended by the 2013/2014 American Society of Clinical Oncology and College of American Pathologists guidelines, appropriate? Findings In this study, chromosome 17 p-arm genomic sites had a high rate of heterozygous deletions, both in the publicly available Molecular Taxonomy of Breast Cancer International Consortium database and in the Breast Cancer International Research Group-005 clinical trial samples using fluorescence in situ hybridization. Meaning The indiscriminate use of alternative controls to assess HER2 status with HER2 -to-control gene ratios by ISH may lead to false-positive determinations and should be avoided, as recommended by the 2018 clinical practice update.

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Impact of an alternative chromosome 17 probe and the 2013 American Society of Clinical Oncology and College of American Pathologists guidelines on fluorescence in situ hybridization for the determination of HER2 gene amplification in breast cancer

Cited by 28 publications

References 41 publications

Double-Equivocal HER2 Invasive Breast Carcinomas: Institutional Experience and Review of Literature

Double-Equivocal HER2 Invasive Breast Carcinomas: Institutional Experience and Review of Literature

Utility of Alternate, Noncentromeric Chromosome 17 Reference Probe for Human Epidermal Growth Factor Receptor Fluorescence In Situ Hybridization Testing in Breast Cancer Cases

Assessment ofERBB2/HER2Status inHER2-Equivocal Breast Cancers by FISH and 2013/2014 ASCO-CAP Guidelines

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