Chromosome 17 polysomy: correlation with histological parameters and<i>HER2NEU</i>gene amplification

­Orsaria, Maria; Khelifa, Sihem; Buza, Natália; Kamath, Anitha; Hui, Pei

doi:10.1136/jclinpath-2013-201506

Cited by 13 publications

(8 citation statements)

References 38 publications

(57 reference statements)

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“…However, CEP17 copy number gain without HER2 gene amplification was not associated with benefit from HER2-targeted therapy in breast cancers [36,37]. Moreover, CEP17 copy number gain in breast cancers has been reported to be associated with adverse clinicopathological features [27,[38][39][40] and response to anthracycline-based therapy in breast cancer [41,42]. However, as for its prognostic significance, there have been conflicting results [43][44][45][46].…”

Section: Complicating Factors For Her2 Interpretationmentioning

confidence: 99%

HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation

Ahn

Woo

Lee

et al. 2020

J Pathol Transl Med

157

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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/ by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Human epidermal growth factor receptor 2 (HER2) is a protooncogene that encodes epidermal growth factor receptor with tyrosine kinase activity, located on chromosome 17 at q21. In breast cancers, HER2 gene is amplified in 15%-20% of invasive breast cancers and its amplification is closely linked to HER2 protein overexpression [1,2]. HER2 amplification is a poor prognostic factor associated with a high rate of recurrence and mortality, and is a predictive factor for response to anthracyclinebased chemotherapies in patients with breast cancer [1,2]. Most importantly, it is a sole predictive marker for treatment benefits from HER2-targeting agents such as trastuzumab, lapatinib, and pertuzumab. As HER2-targeted therapy is exclusively effective in HER2-overexpressed and/or HER2-amplified breast cancers, precise assessment of HER2 status is an essential step for treatment of breast cancer. In this review, we focused on changes in the American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) guidelines on HER2 interpretation and some pitfalls in the interpretation of HER2 status in breast cancers. METHODS OF HER2 TESTINGCurrently, immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and chromogenic in situ hybridization (CISH) including silver in situ hybridization (SISH) are regarded as standard methods for determination of HER2 status in breast cancer, and some of them have been approved by the U.S. Food and Drug Administration (FDA) for HER2 testing in breast cancer since 1998.Although HER2 status can be directly tested by in situ hybridization (ISH), many laboratories have adopted IHC as a screening test, and FISH as a confirmation test for HER2 IHC equivocal cases, considering higher failure rate, longer procedure time and higher reagent cost of FISH, compared to that of IHC. Moreover, Human epidermal growth factor receptor 2 (HER2) protein overexpression and/or HER2 gene amplification is found in about 20% of invasive breast cancers. It is a sole predictive marker for treatment benefits from HER2 targeted therapy and thus, HER2 testing is a routine practice for newly diagnosed breast cancer in pathology. Currently, HER2 immunohistochemistry (IHC) is used for a screening test, and in situ hybridization is used as a confirmation test for HER2 IHC equivocal cases. Since the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines on HER2 testing was first released in 2007, it has been updated to provide clear instructions for HER2 testing and accurate determination of HER2 status in breast cancer. During HER2 interpretation, some pitfalls such as intratumoral HER2 heterogeneity and increase in chromosome enumeration probe 17 signals m...

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Section: Complicating Factors For Her2 Interpretationmentioning

confidence: 99%

HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation

Ahn

Woo

Lee

et al. 2020

J Pathol Transl Med

157

View full text Add to dashboard Cite

show abstract

“…We read with interest the article by Orsaria et al 1 on chromosome 17 ‘polysomy’ in invasive breast carcinoma, and its correlation with histological parameters and HER2 gene amplification. Although the authors mentioned briefly that ‘a simple increase of CEP17 copy number does not necessarily represent the presence of multiple copies of chromosome 17’ and that ‘focal pericentromeric gain or partial polysomy has been shown to exist in a majority of the so-called polysomy 17 cases’, they consistently use the term ‘polysomy 17’ throughout their manuscript, whereas, their definition of polysomy is based on the presence of ≥3 CEP17 signals per nucleus.…”

mentioning

confidence: 99%

CEP17 copy number increase does not indicate polysomy 17

Moelans

Diest

2014

J Clin Pathol

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“…With the inclusion of the control genes TP53 and RARA in the present study, the incidence rate of polysomy was ~0.2% (3/1518), suggesting that true polysomy was less common than what was previously observed in the literature. In cases where increased levels of polysomy are detected, it may have occurred due to CEP17 amplification, as suggested by Zeng et al ( 19 ), whereas decreases in polysomy incidence rate may be caused by the section thickness being less than the diameter of cells ( 20 , 21 ). Chromosome 17 polysomy may indicate poor efficacy of cytotoxic medicines, leading to tumor metastasis ( 22 , 23 ), on the basis of which Herceptin and/or anthracyclines may be more suitable.…”

Section: Discussionmentioning

confidence: 93%

Retrospective analysis of the association between human epidermal growth factor receptor 2 amplification and chromosome enumeration probe 17 status in patients with breast cancer

Dong

et al. 2017

Oncol Lett

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The aim of the present study was to identify potential human epidermal growth factor receptor 2 (HER2) amplification, according to American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) 2013 HER2 testing guidelines, in patients previously determined not to possess HER2 amplification, in accordance with previous 2007 guidelines. Potential discrepancies may arise from chromosome enumeration probe 17 (CEP17) amplification, deletion, polysomyor monosomy. HER2, CEP17, tumor protein p53 (TP53) and retinoic acid receptor α (RARA) genes from 67 patient specimens with suspected amplification, polysomy or monosomy of CEP17 were analyzed using fluorescence in situ hybridization. HER2 status was interpreted using 2007 and 2013 ASCO HER2 test guidelines as well as the reference genes TP53 and RARA. According to ASCO/CAP2007 HER2 guidelines, 20 patients exhibited HER2 amplification (29.85%), 41 were without HER2 amplification (including 25 with polysomy, 15 with monosomy and 1 with suspected monosomy plus co-amplification of HER2 and CEP17) and the remaining 6 patients were equivocal. Using ASCO/CAP 2013 HER2 guidelines, 49 patients exhibited HER2 gene amplification (73.1%). The 29-patient increase included 6 originally at equivocal levels but now demonstrating amplification, 22 originally with polysomy but now revealing co-amplification, and 1 with suspected monosomy plus co-amplification of HER2 and CEP17. According to TP53 and RARA, HER2 was amplified in 43 patients (64.1%). Using the revised guidelines, HER2, originally identified as amplified in 6 patients, was not amplified following the introduction of TP53 and RARA control genes. Among these 6, 4 possessed normal TP53 and RARA. The incidence of co-amplification of HER2 and CEP17 was 1.4% (21/1,518). RARA and TP53 are suitable control genes to evaluate HER2 status.

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Chromosome 17 polysomy: correlation with histological parameters andHER2NEUgene amplification

Abstract: In the absence of the gene amplification, HER2 protein overexpression may be explained by other mechanisms including polysomy 17.

Cited by 13 publications

References 38 publications

HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation

HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation

CEP17 copy number increase does not indicate polysomy 17

Retrospective analysis of the association between human epidermal growth factor receptor 2 amplification and chromosome enumeration probe 17 status in patients with breast cancer

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