PMID- 35970977
OWN - NLM
STAT- MEDLINE
DCOM- 20221108
LR  - 20221108
IS  - 1432-2307 (Electronic)
IS  - 0945-6317 (Print)
IS  - 0945-6317 (Linking)
VI  - 481
IP  - 5
DP  - 2022 Nov
TI  - Comparison of HercepTest mAb pharmDx (Dako Omnis, GE001) with Ventana PATHWAY 
      anti-HER-2/neu (4B5) in breast cancer: correlation with HER2 amplification and 
      HER2 low status.
PG  - 685-694
LID - 10.1007/s00428-022-03378-5 [doi]
AB  - Performance of the new CE-IVD-marked HercepTest mAb pharmDx (Dako Omnis) assay 
      (HercepTest (mAb)) was compared against the PATHWAY(R) anti-HER-2/neu (4B5) 
      (PATHWAY 4B5) assay using 119 pre-selected breast cancer samples covering the 
      entire range of HER2 immunohistochemistry (IHC) expression scores (0, 1 + , 2 + , 
      3 +). The sensitivity and specificity of both assays were assessed based on 
      consensus IHC scores and amplification status, as determined by fluorescence in 
      situ hybridization (FISH) according to 2018 ASCO/CAP testing guidelines. There 
      was a high concordance between results from the HercepTest (mAb) and PATHWAY 4B5 
      assays for HER2-negative (IHC 0, 1 + , 2 + and FISH negative) and HER2-positive 
      (IHC 3 + , 2 + and FISH positive) breast carcinomas (98.2%). Regarding individual 
      IHC scores, complete agreement was achieved in 69.7% (83/119) of cases, and all 
      but one of the discordant cases were due to higher HER2-status scoring using the 
      HercepTest (mAb). Thus, more tumors were overscored as IHC 2 + by HercepTest 
      (mAb) (27 versus 15) as evidenced by their lower FISH positivity rate (48.1% 
      versus 80%). However, two amplified tumors identified as IHC 2 + by HercepTest 
      (mAb) were missed by PATHWAY 4B5 (IHC 1 +). Four additional cases identified as 
      IHC 2 + by HercepTest (mAb), with FISH ratio < 2 but elevated gene counts (>/= 4 
      to < 6), were recorded negative by PATHWAY 4B5. The HercepTest (mAb) detects HER2 
      expression with higher sensitivity in tumors with gene amplification (ISH group 
      1) and increased gene counts (ISH group 4) as well as in HER2-low tumors (HER2 
      IHC2 + /FISH negative or IHC 1 +). Future studies will demonstrate whether this 
      translates into improved patient selection especially for new HER2-directed 
      therapies.
CI  - (c) 2022. The Author(s).
FAU - Ruschoff, Josef
AU  - Ruschoff J
AD  - Targos - A Discovery Life Sciences Company, Germaniastrasse 7, 34119, Kassel, 
      Germany. josef.rueschoff@dls.com.
FAU - Friedrich, Michael
AU  - Friedrich M
AD  - Targos - A Discovery Life Sciences Company, Germaniastrasse 7, 34119, Kassel, 
      Germany.
FAU - Nagelmeier, Iris
AU  - Nagelmeier I
AD  - Institute of Pathology Nordhessen, Germaniastrasse 7, 34119, Kassel, Germany.
FAU - Kirchner, Matthias
AU  - Kirchner M
AD  - Institute of Pathology Nordhessen, Germaniastrasse 7, 34119, Kassel, Germany.
FAU - Andresen, Lena M
AU  - Andresen LM
AD  - Agilent Technologies Denmark Aps, Produktionsvej 42, 2600, Glostrup, Denmark.
FAU - Salomon, Karin
AU  - Salomon K
AD  - Agilent Technologies Denmark Aps, Produktionsvej 42, 2600, Glostrup, Denmark.
FAU - Portier, Bryce
AU  - Portier B
AD  - Agilent Technologies Inc, 5301 Stevens Creek Blvd, Santa Clara, CA, 95051, USA.
FAU - Sredni, Simone T
AU  - Sredni ST
AD  - Agilent Technologies Inc, 5301 Stevens Creek Blvd, Santa Clara, CA, 95051, USA.
FAU - Schildhaus, Hans Ulrich
AU  - Schildhaus HU
AD  - Targos - A Discovery Life Sciences Company, Germaniastrasse 7, 34119, Kassel, 
      Germany.
AD  - Institute of Pathology Nordhessen, Germaniastrasse 7, 34119, Kassel, Germany.
FAU - Jasani, Bharat
AU  - Jasani B
AD  - Targos - A Discovery Life Sciences Company, Germaniastrasse 7, 34119, Kassel, 
      Germany.
FAU - Grzelinski, Marius
AU  - Grzelinski M
AD  - Targos - A Discovery Life Sciences Company, Germaniastrasse 7, 34119, Kassel, 
      Germany.
FAU - Viale, Giuseppe
AU  - Viale G
AD  - IEO European Institute of Oncology IRCCS, and University of Milan, Milan, Italy.
LA  - eng
PT  - Journal Article
DEP - 20220816
PL  - Germany
TA  - Virchows Arch
JT  - Virchows Archiv : an international journal of pathology
JID - 9423843
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Humans
MH  - Female
MH  - *Receptor, ErbB-2/metabolism
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Immunohistochemistry
MH  - *Breast Neoplasms/pathology
MH  - Gene Amplification
PMC - PMC9636083
OTO - NOTNLM
OT  - Dako Omnis
OT  - FISH
OT  - HER2
OT  - HercepTest (mAb)
OT  - IHC
OT  - Invasive breast carcinoma
OT  - PATHWAY 4B
COIS- LMA and KS are employees and shareholders of Agilent Technologies Denmark Aps. BP 
      and STS are employees and shareholders by Agilent Technologies Inc., USA. BJ and 
      GV have acted as a consultant for Agilent Technologies Denmark Aps. Honoraria for 
      lectures and advisory boards have been received by JR from MSD/Merck, GSK, BMS, 
      AstraZeneca, Roche, Exact Sciences, QuIP GmbH; HUS from MSD, BMS, Pfizer, 
      Novartis Oncology, Roche Pharma, Molecular Health; GV from Roche, AstraZeneca, 
      MSD, Pfizer, Novartis, Daiichi Sankyo.
EDAT- 2022/08/16 06:00
MHDA- 2022/11/09 06:00
PMCR- 2022/08/16
CRDT- 2022/08/15 23:23
PHST- 2022/03/31 00:00 [received]
PHST- 2022/07/06 00:00 [accepted]
PHST- 2022/06/30 00:00 [revised]
PHST- 2022/08/16 06:00 [pubmed]
PHST- 2022/11/09 06:00 [medline]
PHST- 2022/08/15 23:23 [entrez]
PHST- 2022/08/16 00:00 [pmc-release]
AID - 10.1007/s00428-022-03378-5 [pii]
AID - 3378 [pii]
AID - 10.1007/s00428-022-03378-5 [doi]
PST - ppublish
SO  - Virchows Arch. 2022 Nov;481(5):685-694. doi: 10.1007/s00428-022-03378-5. Epub 
      2022 Aug 16.