PMID- 15140287
OWN - NLM
STAT- MEDLINE
DCOM- 20040729
LR  - 20231024
IS  - 1526-8209 (Print)
IS  - 1526-8209 (Linking)
VI  - 5
IP  - 1
DP  - 2004 Apr
TI  - HER2 amplification ratios by fluorescence in situ hybridization and correlation 
      with immunohistochemistry in a cohort of 6556 breast cancer tissues.
PG  - 63-9
AB  - To analyze HER2 amplification in a large cohort of diagnostic breast cancer 
      specimens, fluorescence in situ hybridization (FISH) and immunohistochemistry 
      (IHC) were performed on the same specimens with use of Food and Drug 
      Administration&approved products. Procedures were standardized following the 
      manufacturers' recommendations. Of 116,736 IHC specimens, 20% were positive for 
      HER2. In 16,092 FISH specimens, 22.7% showed HER2 amplification. In the subset of 
      6556 tissues analyzed with IHC and FISH, however, 59% were positive on IHC and 
      23.6% were amplified on FISH. The increased frequency of positive test results is 
      skewed by more frequent reflex FISH testing. In general, expression and 
      amplification trended together, with the least amplification (4.1%) seen in 
      IHC-negative cases, 7.4% amplification seen in IHC 1+ cases, 23.3% amplification 
      seen in IHC 2+ cases, and 91.7% amplification seen in IHC 3+ cases. When FISH 
      amplification ratios were stratified, the low FISH ratios (2.0-2.2) were most 
      frequently seen in specimens with negative IHC results, high ratios (>5.0) were 
      seen in IHC 3+ specimens, and intermediate levels of amplification were similar 
      for all levels of IHC. The effect of changing the cutoff point was analyzed: 
      removing cases with a ratio of exactly 2.0 decreased the FISH positivity rate to 
      22.2% in the combined IHC and FISH cohort. Sequentially moving the cutoff point 
      to 2.2 and 2.5 affected cases at all IHC expression levels. Each change removed 
      approximately 2% from the apparent positivity. This large database provides the 
      distribution frequency of HER2 protein expression and gene amplification in 
      invasive ductal and lobular breast cancer. The relationship between level of HER2 
      amplification and clinical outcome will require reanalysis of pivotal trial data.
FAU - Owens, Marilyn A
AU  - Owens MA
AD  - IMPATH, Inc., Los Angeles, CA 90066, USA. marilyn.owens@impath.com
FAU - Horten, Bruce C
AU  - Horten BC
FAU - Da Silva, Moacyr M
AU  - Da Silva MM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Clin Breast Cancer
JT  - Clinical breast cancer
JID - 100898731
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Breast/chemistry/metabolism/pathology
MH  - Breast Neoplasms/genetics/metabolism/*pathology
MH  - Carcinoma, Ductal, Breast/genetics/metabolism/pathology
MH  - Carcinoma, Lobular/genetics/metabolism/pathology
MH  - Cohort Studies
MH  - Female
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Nucleic Acid Amplification Techniques/*methods
MH  - Prognosis
MH  - Receptor, ErbB-2/analysis/*genetics
EDAT- 2004/05/14 05:00
MHDA- 2004/07/30 05:00
CRDT- 2004/05/14 05:00
PHST- 2004/05/14 05:00 [pubmed]
PHST- 2004/07/30 05:00 [medline]
PHST- 2004/05/14 05:00 [entrez]
AID - S1526-8209(11)70834-5 [pii]
AID - 10.3816/cbc.2004.n.011 [doi]
PST - ppublish
SO  - Clin Breast Cancer. 2004 Apr;5(1):63-9. doi: 10.3816/cbc.2004.n.011.