PMID- 21809992
OWN - NLM
STAT- MEDLINE
DCOM- 20110927
LR  - 20220309
IS  - 1543-2165 (Electronic)
IS  - 0003-9985 (Linking)
VI  - 135
IP  - 8
DP  - 2011 Aug
TI  - Effects of the change in cutoff values for human epidermal growth factor receptor 
      2 status by immunohistochemistry and fluorescence in situ hybridization: a study 
      comparing conventional brightfield microscopy, image analysis-assisted 
      microscopy, and interobserver variation.
PG  - 1010-6
LID - 10.5858/2010-0462-OAR [doi]
AB  - CONTEXT: New guidelines for HER2 testing have been introduced. OBJECTIVES: To 
      evaluate the difference in HER2 assessment after introduction of new cutoff 
      levels for both immunohistochemistry (IHC) and fluorescence in situ hybridization 
      (FISH) and to compare interobserver agreement and time to score between image 
      analysis and conventional microscopy. DESIGN: Samples from 150 patients with 
      breast cancer were scored by 7 pathologists using conventional microscopy, with a 
      cutoff of both 10% and 30% IHC-stained cells, and using automated microscopy with 
      image analysis. The IHC results were compared individually and to HER2 status as 
      determined by FISH, using both the approved cutoff of 2.0 and the recently 
      introduced cutoff of 2.2. RESULTS: High concordance was found in IHC scoring 
      among the 7 pathologists. The 30% cutoff led to slightly fewer positive IHC 
      observations. Introduction of a FISH equivocal zone affected 4% of the FISH 
      scores. If cutoff for FISH is kept at 2.0, no difference in patient selection is 
      found between the 10% and the 30% IHC cutoff. Among the 150 breast cancer 
      samples, the new 30% IHC and 2.2 FISH cutoff levels resulted in one case without 
      a firm diagnosis because both IHC and FISH were equivocal. Automated microscopy 
      and image analysis-assisted IHC led to significantly better interobserver 
      agreement among the 7 pathologists, with an increase in mean scoring time of only 
      about 30 seconds per slide. CONCLUSIONS: The change in cutoff levels led to a 
      higher concordance between IHC and FISH, but fewer samples were classified as 
      HER2 positive.
FAU - Atkinson, Roscoe
AU  - Atkinson R
AD  - Department of Pathology, University of Southern California, Los Angeles, USA.
FAU - Mollerup, Jens
AU  - Mollerup J
FAU - Laenkholm, Anne-Vibeke
AU  - Laenkholm AV
FAU - Verardo, Mark
AU  - Verardo M
FAU - Hawes, Debra
AU  - Hawes D
FAU - Commins, Deborah
AU  - Commins D
FAU - Engvad, Birte
AU  - Engvad B
FAU - Correa, Adrian
AU  - Correa A
FAU - Ehlers, Charlotte Cort
AU  - Ehlers CC
FAU - Nielsen, Kirsten Vang
AU  - Nielsen KV
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PL  - United States
TA  - Arch Pathol Lab Med
JT  - Archives of pathology & laboratory medicine
JID - 7607091
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Breast Neoplasms/genetics/metabolism/pathology
MH  - Female
MH  - Humans
MH  - *Image Processing, Computer-Assisted
MH  - Immunohistochemistry/*methods/standards
MH  - In Situ Hybridization, Fluorescence/*methods/standards
MH  - Observer Variation
MH  - *Receptor, ErbB-2/genetics/metabolism
MH  - Reference Values
MH  - Reproducibility of Results
EDAT- 2011/08/04 06:00
MHDA- 2011/09/29 06:00
CRDT- 2011/08/04 06:00
PHST- 2011/08/04 06:00 [entrez]
PHST- 2011/08/04 06:00 [pubmed]
PHST- 2011/09/29 06:00 [medline]
AID - 10.1043/2010-0462-OAR [pii]
AID - 10.5858/2010-0462-OAR [doi]
PST - ppublish
SO  - Arch Pathol Lab Med. 2011 Aug;135(8):1010-6. doi: 10.5858/2010-0462-OAR.