PMID- 11850542
OWN - NLM
STAT- MEDLINE
DCOM- 20020412
LR  - 20141120
IS  - 0893-3952 (Print)
IS  - 0893-3952 (Linking)
VI  - 15
IP  - 2
DP  - 2002 Feb
TI  - Aneusomy 17 in breast cancer: its role in HER-2/neu protein expression and 
      implication for clinical assessment of HER-2/neu status.
PG  - 137-45
AB  - HER-2/neu protein overexpression in breast cancer is mostly caused by HER-2/neu 
      gene amplification. However, it is unclear whether aneusomy 17 may also play a 
      role. Using immunohistochemistry assay (IHC) with DAKO antibody and manual 
      quantitation, 189 specimens were selected from archival invasive breast cancer 
      specimens, including most IHC-positive and some IHC-negative cases (n = 158 and 
      31, respectively). They were then analyzed by PathVysion fluorescence in situ 
      hybridization (FISH) assay (Vysis, Inc., Downers Grove, IL) and by an image 
      analyzer (ACIS; ChromaVision Medical Systems, Inc., San Juan Capistrano, 
      CA)-assisted IHC quantitation. Ninety-two cases contained disomy 17 (chromosome 
      17 centromere, 1.76-2.25 signals per cell) whereas 97 cases had aneusomy 17, 
      including 82 with low polysomy (2.26-3.75 signals per cell), 10 with high 
      polysomy (> or =3.76 signals per cell), and 5 with hypodisomy (> or =1.75 signals 
      per cell). HER-2/neu protein expression had the highest correlation with 
      HER-2/neu gene dosage (copy number; r =.826), followed by the HER-2/neu gene to 
      chromosome 17 ratio (r =.733). The lowest correlation was with the chromosome 17 
      copy number (r =.307), on which the 10 cases with high polysomy 17 had a 
      disproportionately high impact. The FISH assay using the PathVysion criterion for 
      HER-2/neu gene amplification (HER-2/neu gene to chromosome 17 ratio, > or = 2.00) 
      achieved higher concordance with ACIS IHC than did an alternative FISH criterion 
      (absolute HER-2/neu gene copy number, > or = 4.00 signals per cell). Most ACIS 
      IHC-PathVysion FISH-discordant cases contained disomy or low polysomy 17, whereas 
      all 10 cases with high polysomy 17 had no such discordance. However, two cases 
      with monosomy 17 had ACIS IHC-PathVysion FISH discordance, i.e., with gene 
      amplification, but no protein overexpression. Both cases would have had no gene 
      amplification if the alternative FISH criterion had been used. In conclusion, 
      aneusomy 17 is common in breast cancer. Except in a certain subset of cases, 
      aneusomy 17 probably is not a significant factor for HER-2/neu protein expression 
      or for clinical assessment of HER-2/neu status.
FAU - Wang, Sijian
AU  - Wang S
AD  - Department of Pathology, The University of Texas Southwestern Medical Center, 
      Dallas, Texas 75390-9072, USA.
FAU - Hossein Saboorian, M
AU  - Hossein Saboorian M
FAU - Frenkel, Eugene P
AU  - Frenkel EP
FAU - Haley, Barbara B
AU  - Haley BB
FAU - Siddiqui, Momin T
AU  - Siddiqui MT
FAU - Gokaslan, Sefik
AU  - Gokaslan S
FAU - Hynan, Linda
AU  - Hynan L
FAU - Ashfaq, Raheela
AU  - Ashfaq R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - *Aneuploidy
MH  - Breast Neoplasms/genetics/*pathology
MH  - Chromosomes, Human, Pair 17/*genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Receptor, ErbB-2/*genetics
EDAT- 2002/02/19 10:00
MHDA- 2002/04/16 10:01
CRDT- 2002/02/19 10:00
PHST- 2002/02/19 10:00 [pubmed]
PHST- 2002/04/16 10:01 [medline]
PHST- 2002/02/19 10:00 [entrez]
AID - 10.1038/modpathol.3880505 [doi]
PST - ppublish
SO  - Mod Pathol. 2002 Feb;15(2):137-45. doi: 10.1038/modpathol.3880505.