PMID- 22083232
OWN - NLM
STAT- MEDLINE
DCOM- 20121106
LR  - 20171116
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Linking)
VI  - 133
IP  - 3
DP  - 2012 Jun
TI  - Topoisomerase 2A gene amplification in breast cancer. Critical evaluation of 
      different FISH probes.
PG  - 929-35
LID - 10.1007/s10549-011-1873-8 [doi]
AB  - The HER2 amplicon on chromosome 17q is variable in size and occasionally includes 
      Topoisomerase 2A (TOP2A) at 17q21-22. It has been suggested that TOP2 
      co-amplification, not HER2 amplification on chromosome 17q11.2-12, is a useful 
      predictive marker of response to anthracycline-based chemotherapy in breast 
      cancer patients. Given the significant toxicities of anthracyclines, the 
      detection methods of TOP2A gene amplifications have to be standardized. We 
      determined TOP2A gene alterations using two different fluorescence in situ 
      hybridization (FISH) DNA probes. HER2 amplifications were identified with the 
      PathVysion probe. TOP2A status of 42 HER2 amplified breast cancers was tested by 
      FISH with PathVysion covering 160 kb and DAKO pharm DX covering 228 kb of the 
      TOP2A amplicon. TOP2A protein expression was tested by immunohistochemistry. 
      Multiplex-ligation dependent probe amplification (MLPA) was performed 
      retrospectively in cases showing discrepancies. TOP2A was amplified in 15 of 42 
      cases (35%) with DAKO pharm DX and in 11 of 42 cases (26%) with PathVysion. In 
      all four discrepant cases, MLPA showed no TOP2A amplification, but instead 
      amplification of an upstream region including HER2. TOP2A was deleted in the same 
      seven of 42 carcinomas (17%) with both probes. TOP2A protein expression was 
      detected in all 42 tumours (100%) with high intratumoral heterogeneity. TOP2A 
      amplification rate depends on the length of the hybridized probes for the TOP2A 
      locus. Because TOP2A, not HER2, is a target of anthracyclines, non-overlapping 
      DNA probes should be used to evaluate any associations between such alterations 
      and response to anthracycline-based chemotherapy.
FAU - Varga, Zsuzsanna
AU  - Varga Z
AD  - Department of Pathology, Institute of Surgical Pathology, University Hospital 
      Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland. zsuzsanna.varga@usz.ch
FAU - Moelans, Cathy B
AU  - Moelans CB
FAU - Zuerrer-Hardi, Ursina
AU  - Zuerrer-Hardi U
FAU - Ramach, Constanze
AU  - Ramach C
FAU - Behnke, Silvia
AU  - Behnke S
FAU - Kristiansen, Glen
AU  - Kristiansen G
FAU - Moch, Holger
AU  - Moch H
LA  - eng
PT  - Journal Article
DEP - 20111115
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (DNA Probes)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Poly-ADP-Ribose Binding Proteins)
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  - Antigens, Neoplasm/*genetics/metabolism
MH  - Breast Neoplasms/diagnosis/*genetics/metabolism
MH  - *DNA Probes
MH  - DNA Topoisomerases, Type II/*genetics/metabolism
MH  - DNA-Binding Proteins/*genetics/metabolism
MH  - Female
MH  - *Gene Amplification
MH  - Gene Dosage
MH  - Humans
MH  - *In Situ Hybridization, Fluorescence
MH  - Poly-ADP-Ribose Binding Proteins
MH  - Receptor, ErbB-2/genetics/metabolism
EDAT- 2011/11/16 06:00
MHDA- 2012/11/07 06:00
CRDT- 2011/11/16 06:00
PHST- 2011/09/15 00:00 [received]
PHST- 2011/11/01 00:00 [accepted]
PHST- 2011/11/16 06:00 [entrez]
PHST- 2011/11/16 06:00 [pubmed]
PHST- 2012/11/07 06:00 [medline]
AID - 10.1007/s10549-011-1873-8 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2012 Jun;133(3):929-35. doi: 10.1007/s10549-011-1873-8. 
      Epub 2011 Nov 15.