PMID- 16184453
OWN - NLM
STAT- MEDLINE
DCOM- 20051212
LR  - 20191210
IS  - 0167-6806 (Print)
IS  - 0167-6806 (Linking)
VI  - 93
IP  - 1
DP  - 2005 Sep
TI  - Determination of HER2 gene amplification by fluorescence in situ hybridization 
      and concordance with the clinical trials immunohistochemical assay in women with 
      metastatic breast cancer evaluated for treatment with trastuzumab.
PG  - 3-11
AB  - PURPOSE: To evaluate the concordance between HER2 gene amplification, determined 
      by fluorescence in situ hybridization (FISH), and HER2 protein overexpression 
      assessed by an immunohistochemical (IHC) assay. The IHC protocol used was a 
      research assay, known as the Clinical Trial Assay (CTA), developed to select 
      women with metastatic breast cancer (MBC) for three pivotal clinical trials of 
      trastuzumab therapy. METHODS: A direct-labeled, dual-probe FISH assay was used to 
      determine HER2 amplification in 623 fixed breast cancer tissue specimens. These 
      specimens had been stored as paraffin-embedded sections for 25 years. All 
      specimens had been analyzed for HER2 protein expression by the CTA. To assess the 
      reproducibility of FISH results in archived material, we evaluated a separate 
      group of 617 breast cancer tissue specimens at two different laboratories. 
      RESULTS: Informative FISH results were available for 529 (85%) of the 623 
      specimens. Overall concordance between FISH and IHC results was 82% (95% CI; 
      7885%). Assay agreement between FISH results and specimens with immunostaining 
      scores of 0, 1+, and 3+ were 97, 93 and 89%, respectively. However, only 24% of 
      specimens with 2+ immunostaining scores had HER2 amplification by FISH; there was 
      assay disagreement in 76% of specimens in this IHC subgroup. Interlaboratory FISH 
      concordance was 92% (95% CI; 8994%), indicating very good assay reproducibility 
      in these archived specimens. CONCLUSION: HER2 status determined by CTA-IHC and 
      FISH are significantly correlated; however, differences between these two assays 
      can a ect patient selection for trastuzumab therapy.
FAU - Dybdal, Noel
AU  - Dybdal N
AD  - Genentech Inc., South San Francisco, CA 94080, USA. nod@gene.com
FAU - Leiberman, Grazyna
AU  - Leiberman G
FAU - Anderson, Steven
AU  - Anderson S
FAU - McCune, Bryan
AU  - McCune B
FAU - Bajamonde, Alex
AU  - Bajamonde A
FAU - Cohen, Robert L
AU  - Cohen RL
FAU - Mass, Robert D
AU  - Mass RD
FAU - Sanders, Corsee
AU  - Sanders C
FAU - Press, Michael F
AU  - Press MF
LA  - eng
GR  - CA48780/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Antibodies, Monoclonal/therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/therapeutic use
MH  - Breast Neoplasms/drug therapy/genetics/*metabolism/pathology
MH  - Clinical Trials as Topic
MH  - Female
MH  - Gene Amplification
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, erbB-2/*genetics
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Neoplasm Metastasis
MH  - Paraffin Embedding
MH  - Predictive Value of Tests
MH  - Trastuzumab
EDAT- 2005/09/27 09:00
MHDA- 2005/12/15 09:00
CRDT- 2005/09/27 09:00
PHST- 2005/09/27 09:00 [pubmed]
PHST- 2005/12/15 09:00 [medline]
PHST- 2005/09/27 09:00 [entrez]
AID - 10.1007/s10549-004-6275-8 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2005 Sep;93(1):3-11. doi: 10.1007/s10549-004-6275-8.