PMID- 21698407
OWN - NLM
STAT- MEDLINE
DCOM- 20120822
LR  - 20171116
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Linking)
VI  - 132
IP  - 3
DP  - 2012 Apr
TI  - Co-amplification of the HER2 gene and chromosome 17 centromere: a potential 
      diagnostic pitfall in HER2 testing in breast cancer.
PG  - 925-35
LID - 10.1007/s10549-011-1642-8 [doi]
AB  - Co-amplification of the centromere on chromosome 17 (CEP17) and HER2 can occur in 
      breast cancer. Such aberrant patterns (clusters) on CEP17 can be misleading to 
      calculate the HER2/CEP17 ratio, and thus underreporting of HER2 amplification. We 
      identified 14 breast cancers retrospectively with HER2/CEP17 co-amplification and 
      performed FISH (fluorescence in situ hybridization) with additional chromosome 17 
      probes (17p11.1-q11.1, 17p11.2-p12, TP53 on 17p13.1, RARA on 17q21.1-3 and TOP2 
      on 17q21.3-22) to characterize the spanning of the amplicon in these cases. 
      Furthermore, the HER2 status was analyzed by means of HER2 silver in situ 
      hybridization (SISH) and immunohistochemistry (IHC). The co-amplification of 
      HER2/CEP17 was compared between the three institutions. TP53 was eusomic in all 
      cases, 17p11.2-p12 in 79% (11/14), whereas 17p11.1-q11.1 showed chromosomal gain 
      in all cases. RARA was amplified in 10/14 cases (71%) and TOP2 in 3/14 cases 
      (21%). HER2 was amplified with FISH/SISH in all 14 cases. 9/14 tumors were 3+ IHC 
      positive (64%) and 3 cases were 2+ IHC positive. In our cohort the CEP17 amplicon 
      almost always involves the HER2 but not the TOP2 locus. Overall agreement on 
      HER2/CEP17 ratio (when applying ASCO/CAP guidelines) was only 64% (9/14 cases) 
      between the institutions. Discrepant ratios varied from 1.1 to 14.3. The 
      HER2/CEP17 co-amplification is not defined in the ASCO/CAP guidelines, and may 
      result in inaccurate HER2-FISH/SISH status, particularly if only the calculated 
      HER2/CEP17 ratio is reported. It is recommended to report separate CEP17 and HER2 
      signals in complex HER2/CEP17 patterns.
FAU - Varga, Zsuzsanna
AU  - Varga Z
AD  - Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 
      12, 8091 Zurich, Switzerland. zsuzsanna.varga@usz.ch
FAU - Tubbs, Raymond R
AU  - Tubbs RR
FAU - Wang, Zhen
AU  - Wang Z
FAU - Sun, Yang
AU  - Sun Y
FAU - Noske, Aurelia
AU  - Noske A
FAU - Kradolfer, Doris
AU  - Kradolfer D
FAU - Bosshard, Giovanna
AU  - Bosshard G
FAU - Jochum, Wolfram
AU  - Jochum W
FAU - Moch, Holger
AU  - Moch H
FAU - Ohlschlegel, Christian
AU  - Ohlschlegel C
LA  - eng
PT  - Journal Article
DEP - 20110623
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Poly-ADP-Ribose Binding Proteins)
RN  - 0 (RARA protein, human)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 5.99.1.3 (DNA Topoisomerases, Type II)
RN  - EC 5.99.1.3 (TOP2A protein, human)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antigens, Neoplasm/genetics
MH  - Breast Neoplasms/diagnosis/*genetics
MH  - Carcinoma, Ductal, Breast/diagnosis/*genetics
MH  - Centromere/*genetics
MH  - Chromosomes, Human, Pair 17/*genetics
MH  - DNA Copy Number Variations
MH  - DNA Topoisomerases, Type II/genetics
MH  - DNA-Binding Proteins/genetics
MH  - Diagnostic Errors
MH  - Female
MH  - *Gene Amplification
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Middle Aged
MH  - Poly-ADP-Ribose Binding Proteins
MH  - Receptor, ErbB-2/*genetics
MH  - Receptors, Retinoic Acid/genetics
MH  - Retinoic Acid Receptor alpha
MH  - Retrospective Studies
MH  - Tumor Suppressor Protein p53/genetics
EDAT- 2011/06/24 06:00
MHDA- 2012/08/23 06:00
CRDT- 2011/06/24 06:00
PHST- 2011/04/05 00:00 [received]
PHST- 2011/06/13 00:00 [accepted]
PHST- 2011/06/24 06:00 [entrez]
PHST- 2011/06/24 06:00 [pubmed]
PHST- 2012/08/23 06:00 [medline]
AID - 10.1007/s10549-011-1642-8 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2012 Apr;132(3):925-35. doi: 10.1007/s10549-011-1642-8. 
      Epub 2011 Jun 23.