TOP2A amplification in the absence of that of HER-2/neu: toward individualization of chemotherapeutic practice in breast cancer

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.