PMID- 14608539
OWN - NLM
STAT- MEDLINE
DCOM- 20031125
LR  - 20190722
IS  - 0046-8177 (Print)
IS  - 0046-8177 (Linking)
VI  - 34
IP  - 10
DP  - 2003 Oct
TI  - Strong HER-2/neu protein overexpression by immunohistochemistry often does not 
      predict oncogene amplification by fluorescence in situ hybridization.
PG  - 1043-7
AB  - Breast cancer patients with HER-2/neu oncogene amplification by fluorescence in 
      situ hybridization (FISH) have been shown to have a better response to 
      trastuzumab (Herceptin) therapy than those showing HER-2/neu protein 
      overexpression only. Many centers currently perform FISH only on tumors showing 
      2+ HER-2/neu positivity by immunohistochemistry (IHC), with the assumption that 
      3+ positivity virtually equates with amplification. Results of FISH performed on 
      102 breast cancer cases over a 12-month period were correlated with HER-2/neu IHC 
      results. FISH was performed using a ratio of HER-2/neu and chromosome 17 
      centromere signal counts (PathVysion; Vysis, Downers Grove, IL). 
      Immunohistochemical expression of HER-2/neu was evaluated according to the 
      published scoring guidelines of the HercepTest (Dako, Carpinteria, CA). Only 22 
      of 45 tumors with 3+ positivity (49%) showed amplification by FISH. Only 2 of 25 
      cases with 2+ staining by IHC (6%) showed gene amplification, and 1 of 25 cases 
      with negative IHC staining (4%) showed weak amplification. Of the 25 cases 
      showing oncogene amplification, 22 (88%) showed 3+ IHC positivity, 2 (8%) showed 
      2+ positivity, and 1 (4%) was negative by IHC. More than 50% of breast tumors 
      showing strong 3+ HER-2/neu staining do not show oncogene amplification by FISH. 
      Most tumors with 2+ and negative IHC also fail to amplify. In our experience, 
      FISH studies should be performed on all 3+ and 2+ staining tumors to avoid 
      inappropriate and toxic treatment. The decision to perform FISH on IHC-negative 
      tumors should be guided by additional parameters, including tumor grade and 
      estrogen receptor status.
FAU - Hammock, Lauren
AU  - Hammock L
AD  - Department of Pathology and Laboratory Medicine, Emory University Hospital, 
      Atlanta, GA, USA.
FAU - Lewis, Melinda
AU  - Lewis M
FAU - Phillips, Carol
AU  - Phillips C
FAU - Cohen, Cynthia
AU  - Cohen C
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Hum Pathol
JT  - Human pathology
JID - 9421547
RN  - 0 (Reagent Kits, Diagnostic)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
CIN - Hum Pathol. 2004 Feb;35(2):143-6. PMID: 14991529
CIN - Hum Pathol. 2004 Jul;35(7):903-4. PMID: 15257559
MH  - Adenocarcinoma/genetics/*metabolism/secondary
MH  - Breast Neoplasms/genetics/*metabolism/pathology
MH  - Female
MH  - *Gene Amplification
MH  - *Genes, erbB-2
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Reagent Kits, Diagnostic
MH  - Receptor, ErbB-2/genetics/*metabolism
EDAT- 2003/11/11 05:00
MHDA- 2003/12/03 05:00
CRDT- 2003/11/11 05:00
PHST- 2003/11/11 05:00 [pubmed]
PHST- 2003/12/03 05:00 [medline]
PHST- 2003/11/11 05:00 [entrez]
AID - S004681770300409X [pii]
AID - 10.1053/s0046-8177(03)00409-x [doi]
PST - ppublish
SO  - Hum Pathol. 2003 Oct;34(10):1043-7. doi: 10.1053/s0046-8177(03)00409-x.