PMID- 18834223
OWN - NLM
STAT- MEDLINE
DCOM- 20081024
LR  - 20210527
IS  - 1543-2165 (Electronic)
IS  - 0003-9985 (Linking)
VI  - 132
IP  - 10
DP  - 2008 Oct
TI  - Comparison of quantitative immunofluorescence with conventional methods for 
      HER2/neu testing with respect to response to trastuzumab therapy in metastatic 
      breast cancer.
PG  - 1635-47
AB  - CONTEXT: Selection for trastuzumab therapy depends on a companion diagnostic 
      assessment of HER2 by either immunohistochemistry (IHC) for protein 
      overexpression or fluorescence in situ hybridization (FISH) to detect gene 
      amplification. Although many studies have compared IHC to FISH, few have compared 
      the tests to the true gold standard, tumor response. OBJECTIVE: To compare HER2 
      testing by FISH and IHC along with a third immunofluorescence-based assay 
      (automated quantitative analysis-tissue microarray [AQUA-TMA]) and to assess the 
      value of each test for prediction of response to trastuzumab. DESIGN: 
      Immunohistochemistry and FISH assays were done on both whole slides (IHC-WS and 
      FISH-WS) and on TMAs (IHC-TMA and FISH-TMA). AQUA was only done on TMAs 
      (AQUA-TMA). Response was assessed according to modified Response Evaluation 
      Criteria in Solid Tumors. RESULTS: AQUA-TMA scores showed a significant linear 
      relationship to both the FISH signal ratio and IHC scores on whole sections and 
      TMAs. Assay assessment by outcome showed no association between response and 
      FISH-WS ratio (P = .96), FISH-TMA (P = .55), IHC-WS (P = .75), or IHC-TMA (P = 
      .06), but a significant relationship between AQUA score and categoric response 
      was observed (P = .01). Assessed as a function of outcome using models of 
      logistic regression, both AQUA-TMA and IHC-TMA were equally significant (P = 
      .01). FISH-WS was the most sensitive assay, with a significantly higher 
      true-positive fraction than all other tests except AQUA-TMA, although it was the 
      least specific. IHC-TMA was the most specific assay. The lowest misclassification 
      rate was achieved using AQUA-TMA (0.30). CONCLUSIONS: Both AQUA-TMA and IHC-TMA 
      were substantially more predictive than the FISH or IHC-WS tests. Although these 
      results are derived from a small retrospective series, they suggest that accurate 
      measurement of protein expression and unbiased selection of tissue for 
      measurement may be key factors in prediction of response.
FAU - Giltnane, Jennifer M
AU  - Giltnane JM
AD  - Departments of Pathology, Yale University School of Medicine, New Haven, 
      Connecticut 06520-8023 , USA.
FAU - Molinaro, Annette
AU  - Molinaro A
FAU - Cheng, Huan
AU  - Cheng H
FAU - Robinson, Andrew
AU  - Robinson A
FAU - Turbin, Dmitry
AU  - Turbin D
FAU - Gelmon, Karen
AU  - Gelmon K
FAU - Huntsman, David
AU  - Huntsman D
FAU - Rimm, David L
AU  - Rimm DL
LA  - eng
GR  - R33 CA106709/CA/NCI NIH HHS/United States
GR  - S10 RR19895/RR/NCRR NIH HHS/United States
GR  - TG 5T32GM07205/GM/NIGMS NIH HHS/United States
GR  - R33 CA 110511/CA/NCI NIH HHS/United States
GR  - K22CA123146/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Arch Pathol Lab Med
JT  - Archives of pathology & laboratory medicine
JID - 7607091
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/*metabolism/secondary
MH  - Cell Line
MH  - Cricetinae
MH  - Female
MH  - Humans
MH  - Immunohistochemistry/*methods
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Logistic Models
MH  - Middle Aged
MH  - Predictive Value of Tests
MH  - Receptor, ErbB-2/*metabolism
MH  - Retrospective Studies
MH  - Sensitivity and Specificity
MH  - Tissue Array Analysis
MH  - Trastuzumab
MH  - Treatment Outcome
EDAT- 2008/10/07 09:00
MHDA- 2008/10/25 09:00
CRDT- 2008/10/07 09:00
PHST- 2008/03/12 00:00 [accepted]
PHST- 2008/10/07 09:00 [pubmed]
PHST- 2008/10/25 09:00 [medline]
PHST- 2008/10/07 09:00 [entrez]
AID - 2007-0523-OAR2 [pii]
AID - 10.5858/2008-132-1635-COQIWC [doi]
PST - ppublish
SO  - Arch Pathol Lab Med. 2008 Oct;132(10):1635-47. doi: 10.5858/2008-132-1635-COQIWC.