Open AccessTOP2A Amplification in the Absence of That of HER‐2/neu: Toward Individualization of Chemotherapeutic Practice in Breast Cancer
Author(s) -
Glynn Ronan W.,
Mahon Sarah,
Curran Catherine,
Callagy Grace,
Miller Nicola,
Kerin Michael J.
Publication year - 2011
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2011-0071
Subject(s) - medicine , breast cancer , cancer , oncology , her2/neu , chemotherapeutic drugs , cancer research
Primary objective. To investigate the relationship between human epidermal growth factor receptor (HER)‐2/ neu and the gene encoding topoisomerase IIα ( 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 .