PMID- 15891995
OWN - NLM
STAT- MEDLINE
DCOM- 20050613
LR  - 20171116
IS  - 0046-8177 (Print)
IS  - 0046-8177 (Linking)
VI  - 36
IP  - 4
DP  - 2005 Apr
TI  - The incidence of topoisomerase II-alpha genomic alterations in adenocarcinoma of 
      the breast and their relationship to human epidermal growth factor receptor-2 
      gene amplification: a fluorescence in situ hybridization study.
PG  - 348-56
AB  - Clinical and in vitro evidence supports the concept that human epidermal growth 
      factor receptor-2 ( HER2 ) gene amplification prediction of response to 
      anthracycline-based chemotherapy in breast cancer is not a direct effect of HER2 
      overexpression, but the result of coamplification of topoisomerase II-alpha ( 
      TOP2A ). We investigated the relationship of TOP2A to HER2 genomic alterations by 
      fluorescence in situ hybridization (FISH) and the correlations with polysomic 
      states for chromosome 17 (CEP17). One hundred thirty-eight cases of breast cancer 
      HER2 gene amplified by 2-color FISH ( HER2 /CEP17) were reevaluated with a 
      3-color probe set ( HER2 /CEP17/ TOP2A ) to investigate the frequency of 
      coamplification and deletion of TOP2A . TOP2A was never amplified in the absence 
      of HER2 amplification and was coamplified with HER2 in 68 (50%) of 137 cases; 
      HER2 gene copy number was higher than the TOP2A copy number ( P < .01). Of the 
      137 cases with HER2 amplification, 23 (16%) showed a monoallelic deletion of 
      TOP2A . Of the 43 cases not amplified for HER2 , 27 (63%) were CEP17 eusomic, 13 
      (30%) polysomic, and 3 (7%) monosomic. Of the HER2 nonamplified cases, 2 (5%) 
      showed monoallelic deletion of both the HER2 and TOP2A . The current study 
      demonstrates the complex interrelationship between the HER2 and TOP2A genes in 
      breast cancer. The clinical implications of TOP2A amplification and deletion in 
      breast cancer need to be further defined. If TOP2A gene dosage can be confirmed 
      to correlate with tumor responsiveness to anthracycline-based therapy in the 
      clinical setting, FISH testing for TOP2A status may be warranted to aid in the 
      selection of the most appropriate therapy.
FAU - Hicks, David G
AU  - Hicks DG
AD  - Department of Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, OH 
      44195, USA.
FAU - Yoder, Brian J
AU  - Yoder BJ
FAU - Pettay, James
AU  - Pettay J
FAU - Swain, Eric
AU  - Swain E
FAU - Tarr, Shannon
AU  - Tarr S
FAU - Hartke, Marybeth
AU  - Hartke M
FAU - Skacel, Marek
AU  - Skacel M
FAU - Crowe, Joseph P
AU  - Crowe JP
FAU - Budd, G Thomas
AU  - Budd GT
FAU - Tubbs, Raymond R
AU  - Tubbs RR
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Hum Pathol
JT  - Human pathology
JID - 9421547
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Poly-ADP-Ribose Binding Proteins)
RN  - EC 5.99.1.3 (DNA Topoisomerases, Type II)
RN  - EC 5.99.1.3 (TOP2A protein, human)
SB  - IM
MH  - Adenocarcinoma/*genetics
MH  - Aneuploidy
MH  - Antigens, Neoplasm/*genetics
MH  - Breast Neoplasms/*genetics
MH  - Chromosome Deletion
MH  - *Chromosomes, Human, Pair 17
MH  - DNA Topoisomerases, Type II/*genetics
MH  - DNA-Binding Proteins/*genetics
MH  - Female
MH  - Gene Dosage
MH  - *Genes, erbB-2
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Middle Aged
MH  - Poly-ADP-Ribose Binding Proteins
EDAT- 2005/05/14 09:00
MHDA- 2005/06/14 09:00
CRDT- 2005/05/14 09:00
PHST- 2005/05/14 09:00 [pubmed]
PHST- 2005/06/14 09:00 [medline]
PHST- 2005/05/14 09:00 [entrez]
AID - S0046817705000444 [pii]
AID - 10.1016/j.humpath.2005.01.016 [doi]
PST - ppublish
SO  - Hum Pathol. 2005 Apr;36(4):348-56. doi: 10.1016/j.humpath.2005.01.016.