Peer-Reviewed Journal Details
Mandatory Fields
Glynn, RW;Mahon, S;Curran, C;Callagy, G;Miller, N;Kerin, MJ
2011
July
Oncologist
TOP2A Amplification in the Absence of That of HER-2/neu: Toward Individualization of Chemotherapeutic Practice in Breast Cancer
Published
WOS: 10 ()
Optional Fields
TOPOISOMERASE-II-ALPHA ADJUVANT CHEMOTHERAPY GENE AMPLIFICATION HER2 ANTHRACYCLINES CYCLOPHOSPHAMIDE METHOTREXATE DOXORUBICIN EPIRUBICIN EXPRESSION
16
949
955
Primary objective. To investigate the relationship between human epidermal growth factor receptor (HER)-2/neu and the gene encoding topoisomerase II alpha (TOP2A) in breast cancer, while elucidating their association with clinicopathological variables.Methods. Real-time quantitative polymerase chain reaction (RQ-PCR) was performed on a 96-patient study group to assess gene amplification, and levels were determined using the comparative cycle threshold approach and Taqman assays. An immunohistochemistry (IHC) microarray (n = 76) was then employed to check for correlation between gene amplification and protein expression levels.Results. Amplification levels of TOP2A did not differ significantly according to HER-2/neu status by either RQ-PCR or IHC microarray. Of the HER-2/neu(-) patients, 29.1% demonstrated levels of TOP2A above the third quartile, whereas 22.9% of the HER-2/neu(+) patients had values in the first quartile (log TOP2A < 0.62), thereby indicating low-level amplification. Of the 60 patients characterized as HER-2/neu(-) using IHC and fluorescence in situ hybridization (FISH), 22.9% were classified as TOP2A(+) on the IHC microarray. Of the 14 patients deemed HER-2/neu(+) using IHC and FISH, meanwhile, the majority (n = 10) were classified as TOP2A(+).Conclusions. Our results indicate that amplification of TOP2A in breast cancer is not confined to those who are concomitantly HER-2/neu(+), and suggest that a significant proportion of HER-2/neu(-) patients exhibit high levels of TOP2A. The Oncologist 2011;16:949-955
1083-7159
10.1634/theoncologist.2011-0071
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