HER2 copy number determination in breast cancer using the highly sensitive droplet digital PCR method

Alinger-Scharinger Beate; Kronberger Cornelia; Hutarew Georg; Hitzl Wolfgang; Reitsamer Roland; Klaassen-Federspiel Frederike; Hager Martina; Fischer Thorsten; Sotlar Karl; Jaksch-Bogensperger Heidi

doi:10.1007/s00428-023-03706-3

HER2 copy number determination in breast cancer using the highly sensitive droplet digital PCR method

Alinger-Scharinger Beate^* (Erstautor/-in), Kronberger Cornelia (Co-Autor/-in), Hutarew Georg (Co-Autor/-in), Hitzl Wolfgang (Co-Autor/-in), Reitsamer Roland (Co-Autor/-in), Klaassen-Federspiel Frederike (Co-Autor/-in), Hager Martina (Co-Autor/-in), Fischer Thorsten (Co-Autor/-in), Sotlar Karl (Co-Autor/-in), Jaksch-Bogensperger Heidi (Letztautor/-in)

^*Korrespondierende/r Autor/-in für diese Arbeit

Publikation: Beitrag in Fachzeitschrift › Originalarbeit (Zeitschrift) › Begutachtung

Abstract

Human epidermal growth factor receptor 2 (HER)-positive breast cancer (BC) is characterized by an aggressive clinical course. In the case of HER2 overexpression/amplification, patients benefit from HER2-targeting therapies. Standardized diagnostic HER2 assessment includes immunohistochemistry (IHC) and/or in situ hybridization (ISH). The aim of this study was to compare this "gold standard" with the Droplet Digital™ polymerase chain reaction (ddPCR), a method that allows sensitive and precise detection of copy number variations (CNV) in FFPE (formalin-fixed, paraffin-embedded) DNA samples. Partitioning of the PCR reaction into 20,000 droplets enables a precise quantitative "CN" discrimination also in heterogeneous samples. FFPE breast cancer samples (n = 170) with routinely assessed HER2 status by IHC/ISH were retrospectively analyzed using the ddPCR CNV ERBB2 assay. Comparison of HER2 status assessment by the two methods revealed concordant results in 92.9% (158/170) of the cases. Discrepant cases were verified and interpreted. For ddPCR, a cut off value of 3 HER2 copies was set to distinguish between HER2-negative and HER2-positive BC. Results obtained with the ddPCR CNV ERBB2 assay were consistent and reproducible, and serial dilutions demonstrated a high stability and sensitivity of the method. The ddPCR CNV ERBB2 assay may be a specific and convenient tool to quantify HER2 copy numbers in BC samples. In our study, this method showed high reproducibility in accuracy of HER2 assessment compared to IHC/ISH analysis.

Originalsprache	Englisch
Fachzeitschrift	VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY
DOIs	https://doi.org/10.1007/s00428-023-03706-3
Publikationsstatus	Elektronische Veröffentlichung vor Drucklegung - 23 Nov. 2023

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10.1007/s00428-023-03706-3

1 Korrektur

Correction to: HER2 copy number determination in breast cancer using the highly sensitive droplet digital PCR method
Alinger-Scharinger, B. (Erstautor/-in), Kronberger, C. (Co-Autor/-in), Hutarew, G. (Co-Autor/-in), Hitzl, W. (Co-Autor/-in), Reitsamer, R. (Co-Autor/-in), Klaassen Federspiel, F. (Co-Autor/-in), Hager, M. (Co-Autor/-in), Fischer, T. (Co-Autor/-in), Sotlar, K. (Co-Autor/-in) & Jaksch-Bogensperger, H. (Letztautor/-in), 7 Dez. 2023, in: VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY . 1 S.
Publikation: Beitrag in Fachzeitschrift › Korrektur › Begutachtung

Open Access

1 Abgeschlossen

Her2 monitoring in FFPE samples and liquid biopsies of breast cancer patients using the new and highly sensitive droplet digital PCR method
Alinger-Scharinger, B. (CoPI) & Jaksch-Bogensperger, H. (Weitere Forschende)
1/12/18 → 1/12/19
Projekt: Forschung

Dieses zitieren

Beate, A.-S., Cornelia, K., Georg, H., Wolfgang, H., Roland, R., Frederike, K.-F., Martina, H., Thorsten, F., Karl, S., & Heidi, J.-B. (2023). HER2 copy number determination in breast cancer using the highly sensitive droplet digital PCR method. VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY Vorzeitige Online-Publikation. https://doi.org/10.1007/s00428-023-03706-3

Beate, Alinger-Scharinger ; Cornelia, Kronberger ; Georg, Hutarew et al. / HER2 copy number determination in breast cancer using the highly sensitive droplet digital PCR method. in: VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY 2023.

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title = "HER2 copy number determination in breast cancer using the highly sensitive droplet digital PCR method",

abstract = "Human epidermal growth factor receptor 2 (HER)-positive breast cancer (BC) is characterized by an aggressive clinical course. In the case of HER2 overexpression/amplification, patients benefit from HER2-targeting therapies. Standardized diagnostic HER2 assessment includes immunohistochemistry (IHC) and/or in situ hybridization (ISH). The aim of this study was to compare this {"}gold standard{"} with the Droplet Digital{\texttrademark} polymerase chain reaction (ddPCR), a method that allows sensitive and precise detection of copy number variations (CNV) in FFPE (formalin-fixed, paraffin-embedded) DNA samples. Partitioning of the PCR reaction into 20,000 droplets enables a precise quantitative {"}CN{"} discrimination also in heterogeneous samples. FFPE breast cancer samples (n = 170) with routinely assessed HER2 status by IHC/ISH were retrospectively analyzed using the ddPCR CNV ERBB2 assay. Comparison of HER2 status assessment by the two methods revealed concordant results in 92.9% (158/170) of the cases. Discrepant cases were verified and interpreted. For ddPCR, a cut off value of 3 HER2 copies was set to distinguish between HER2-negative and HER2-positive BC. Results obtained with the ddPCR CNV ERBB2 assay were consistent and reproducible, and serial dilutions demonstrated a high stability and sensitivity of the method. The ddPCR CNV ERBB2 assay may be a specific and convenient tool to quantify HER2 copy numbers in BC samples. In our study, this method showed high reproducibility in accuracy of HER2 assessment compared to IHC/ISH analysis.",

author = "Alinger-Scharinger Beate and Kronberger Cornelia and Hutarew Georg and Hitzl Wolfgang and Reitsamer Roland and Klaassen-Federspiel Frederike and Hager Martina and Fischer Thorsten and Sotlar Karl and Jaksch-Bogensperger Heidi",

note = "Alinger-Scharinger, Kronberger, Hutarew, Hager, Sotlar: Department of Pathology, University Hospital and Paracelsus Medical University Salzburg, Muellner Hauptstra{\ss}e 48, 5020, Salzburg, Austria; Hitzl: Research Management and Technology Transfer, Paracelsus Medical University Salzburg, Strubergasse 16, 5020, Salzburg, Austria; Department of Ophthalmology and Optometry, Paracelsus Medical University Salzburg, Muellner Hauptstra{\ss}e 48, 5020, Salzburg, Austria; Research Program Experimental Ophthalmology and Glaucoma Research, Paracelsus Medical University Salzburg, Muellner Hauptstra{\ss}e 48, 5020, Salzburg, Austria; Reitsamer, Klasseen-Federspiel,Thorsten, Jaksch-Bogensperger: Department of Obstetrics and Gynaecology, Clinical Research Center Salzburg (CRCS), University Hospital and Paracelsus Medical University Salzburg, Muellner Hauptstra{\ss}e 48, 5020, Salzburg, Austria",

year = "2023",

month = nov,

day = "23",

doi = "10.1007/s00428-023-03706-3",

language = "English",

journal = "VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY ",

issn = "0945-6317",

}

Beate, A-S, Cornelia, K, Georg, H , Wolfgang, H , Roland, R , Frederike, K-F , Martina, H , Thorsten, F , Karl, S & Heidi, J-B 2023, 'HER2 copy number determination in breast cancer using the highly sensitive droplet digital PCR method', VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY https://doi.org/10.1007/s00428-023-03706-3

HER2 copy number determination in breast cancer using the highly sensitive droplet digital PCR method. / Beate, Alinger-Scharinger (Erstautor/-in); Cornelia, Kronberger (Co-Autor/-in); Georg, Hutarew (Co-Autor/-in) et al.
in: VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY , 23.11.2023.

Publikation: Beitrag in Fachzeitschrift › Originalarbeit (Zeitschrift) › Begutachtung

TY - JOUR

T1 - HER2 copy number determination in breast cancer using the highly sensitive droplet digital PCR method

AU - Beate, Alinger-Scharinger

AU - Cornelia, Kronberger

AU - Georg, Hutarew

AU - Wolfgang, Hitzl

AU - Roland, Reitsamer

AU - Frederike, Klaassen-Federspiel

AU - Martina, Hager

AU - Thorsten, Fischer

AU - Karl, Sotlar

AU - Heidi, Jaksch-Bogensperger

N1 - Alinger-Scharinger, Kronberger, Hutarew, Hager, Sotlar: Department of Pathology, University Hospital and Paracelsus Medical University Salzburg, Muellner Hauptstraße 48, 5020, Salzburg, Austria; Hitzl: Research Management and Technology Transfer, Paracelsus Medical University Salzburg, Strubergasse 16, 5020, Salzburg, Austria; Department of Ophthalmology and Optometry, Paracelsus Medical University Salzburg, Muellner Hauptstraße 48, 5020, Salzburg, Austria; Research Program Experimental Ophthalmology and Glaucoma Research, Paracelsus Medical University Salzburg, Muellner Hauptstraße 48, 5020, Salzburg, Austria; Reitsamer, Klasseen-Federspiel,Thorsten, Jaksch-Bogensperger: Department of Obstetrics and Gynaecology, Clinical Research Center Salzburg (CRCS), University Hospital and Paracelsus Medical University Salzburg, Muellner Hauptstraße 48, 5020, Salzburg, Austria

PY - 2023/11/23

Y1 - 2023/11/23

N2 - Human epidermal growth factor receptor 2 (HER)-positive breast cancer (BC) is characterized by an aggressive clinical course. In the case of HER2 overexpression/amplification, patients benefit from HER2-targeting therapies. Standardized diagnostic HER2 assessment includes immunohistochemistry (IHC) and/or in situ hybridization (ISH). The aim of this study was to compare this "gold standard" with the Droplet Digital™ polymerase chain reaction (ddPCR), a method that allows sensitive and precise detection of copy number variations (CNV) in FFPE (formalin-fixed, paraffin-embedded) DNA samples. Partitioning of the PCR reaction into 20,000 droplets enables a precise quantitative "CN" discrimination also in heterogeneous samples. FFPE breast cancer samples (n = 170) with routinely assessed HER2 status by IHC/ISH were retrospectively analyzed using the ddPCR CNV ERBB2 assay. Comparison of HER2 status assessment by the two methods revealed concordant results in 92.9% (158/170) of the cases. Discrepant cases were verified and interpreted. For ddPCR, a cut off value of 3 HER2 copies was set to distinguish between HER2-negative and HER2-positive BC. Results obtained with the ddPCR CNV ERBB2 assay were consistent and reproducible, and serial dilutions demonstrated a high stability and sensitivity of the method. The ddPCR CNV ERBB2 assay may be a specific and convenient tool to quantify HER2 copy numbers in BC samples. In our study, this method showed high reproducibility in accuracy of HER2 assessment compared to IHC/ISH analysis.

AB - Human epidermal growth factor receptor 2 (HER)-positive breast cancer (BC) is characterized by an aggressive clinical course. In the case of HER2 overexpression/amplification, patients benefit from HER2-targeting therapies. Standardized diagnostic HER2 assessment includes immunohistochemistry (IHC) and/or in situ hybridization (ISH). The aim of this study was to compare this "gold standard" with the Droplet Digital™ polymerase chain reaction (ddPCR), a method that allows sensitive and precise detection of copy number variations (CNV) in FFPE (formalin-fixed, paraffin-embedded) DNA samples. Partitioning of the PCR reaction into 20,000 droplets enables a precise quantitative "CN" discrimination also in heterogeneous samples. FFPE breast cancer samples (n = 170) with routinely assessed HER2 status by IHC/ISH were retrospectively analyzed using the ddPCR CNV ERBB2 assay. Comparison of HER2 status assessment by the two methods revealed concordant results in 92.9% (158/170) of the cases. Discrepant cases were verified and interpreted. For ddPCR, a cut off value of 3 HER2 copies was set to distinguish between HER2-negative and HER2-positive BC. Results obtained with the ddPCR CNV ERBB2 assay were consistent and reproducible, and serial dilutions demonstrated a high stability and sensitivity of the method. The ddPCR CNV ERBB2 assay may be a specific and convenient tool to quantify HER2 copy numbers in BC samples. In our study, this method showed high reproducibility in accuracy of HER2 assessment compared to IHC/ISH analysis.

U2 - 10.1007/s00428-023-03706-3

DO - 10.1007/s00428-023-03706-3

M3 - Original Article (Journal)

C2 - 37996704

SN - 0945-6317

JO - VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY

JF - VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY

ER -

Beate AS, Cornelia K, Georg H , Wolfgang H , Roland R , Frederike KF et al. HER2 copy number determination in breast cancer using the highly sensitive droplet digital PCR method. VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY . 2023 Nov 23. Epub 2023 Nov 23. doi: 10.1007/s00428-023-03706-3

HER2 copy number determination in breast cancer using the highly sensitive droplet digital PCR method

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Correction to: HER2 copy number determination in breast cancer using the highly sensitive droplet digital PCR method

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Her2 monitoring in FFPE samples and liquid biopsies of breast cancer patients using the new and highly sensitive droplet digital PCR method

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