PMID- 17041102
OWN - NLM
STAT- MEDLINE
DCOM- 20070130
LR  - 20200930
IS  - 1535-7163 (Print)
IS  - 1535-7163 (Linking)
VI  - 5
IP  - 10
DP  - 2006 Oct
TI  - Correction for chromosome-17 is critical for the determination of true Her-2/neu 
      gene amplification status in breast cancer.
PG  - 2572-9
AB  - PURPOSE: Trastuzumab is the cornerstone for treatment of women with 
      HER2-overexpressing breast cancer, both in the adjuvant and in the metastatic 
      settings. The accurate assessment of HER2 is, therefore, critical to identifying 
      patients who may benefit from trastuzumab-based therapy. This project aimed to 
      determine the optimal scoring method for fluorescence in situ hybridization 
      (FISH) assay. METHODS: FISH assay was done on 893 samples of breast cancer. Three 
      scoring methods were evaluated: Her2/CEP17> or =2, Her2>4, or Her2>6. Protein and 
      gene expression were evaluated by immunohistochemistry (n = 584) and 
      mRNA/assay/nucleic acid sequence-based amplification (NASBA; n = 90). RESULTS: 
      Samples were divided into five groups based on FISH results: disomic amplified 
      and nonamplified, polysomic amplified, nonamplified, and discordant (10.8% of 
      cases, mostly positive with Her2>4 scoring, but negative with the others). 
      Her2/CEP17> or =2 and Her2>6 scoring methods showed the best association (a) with 
      regard to FISH scoring (kappa = 0.906, P < 10(-6)) and (b) between FISH and 
      immunohistochemistry (3+ as positive; kappa > 0.650, P < 10(-6)) or NASBA (kappa 
      > 0.536, P < 10(-6)). Polysomy had an effect on Her2 copy number (P < 10(-6)), 
      but had no effect on protein and mRNA content. Therefore, within the discordant 
      subgroup, for which additive Her-2 gene copies are due to high polysomy, protein 
      and mRNA levels were similar to those of the nonamplified samples. For this 
      subgroup, the best concordance between FISH/immunohistochemistry/NASBA was 
      observed with the Her2/CEP17 ratio and Her-2>6 scoring (68% and 58% perfect 
      matches, respectively). No perfect matches were observed using the Her2>4 scoring 
      method. CONCLUSION: Correction for chromosome-17 is the method of choice for 
      clinical practice; Her-2>6, but not Her-2>4, could be used as an alternative.
FAU - Dal Lago, Lissandra
AU  - Dal Lago L
AD  - Translational Research Unit, Bordet Institute, Brussels, Belgium.
FAU - Durbecq, Virginie
AU  - Durbecq V
FAU - Desmedt, Christine
AU  - Desmedt C
FAU - Salgado, Roberto
AU  - Salgado R
FAU - Verjat, Thibault
AU  - Verjat T
FAU - Lespagnard, Laurence
AU  - Lespagnard L
FAU - Ma, Yan
AU  - Ma Y
FAU - Veys, Isabelle
AU  - Veys I
FAU - Di Leo, Angelo
AU  - Di Leo A
FAU - Sotiriou, Christos
AU  - Sotiriou C
FAU - Piccart, Martine
AU  - Piccart M
FAU - Larsimont, Denis
AU  - Larsimont D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cancer Ther
JT  - Molecular cancer therapeutics
JID - 101132535
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Aneuploidy
MH  - Breast Neoplasms/*genetics/metabolism
MH  - Chromosomes, Human, Pair 17/*genetics
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Nucleic Acid Amplification Techniques
MH  - RNA, Messenger/biosynthesis
MH  - Receptor, ErbB-2/biosynthesis/*genetics
EDAT- 2006/10/17 09:00
MHDA- 2007/01/31 09:00
CRDT- 2006/10/17 09:00
PHST- 2006/10/17 09:00 [pubmed]
PHST- 2007/01/31 09:00 [medline]
PHST- 2006/10/17 09:00 [entrez]
AID - 5/10/2572 [pii]
AID - 10.1158/1535-7163.MCT-06-0129 [doi]
PST - ppublish
SO  - Mol Cancer Ther. 2006 Oct;5(10):2572-9. doi: 10.1158/1535-7163.MCT-06-0129.