TOP2A Amplification in the Absence of That of HER-2/neu: Toward Individualization of Chemotherapeutic Practice in Breast Cancer
Menée sur 96 patientes, cette étude montre qu'une amplification du gène TOP2A n'est pas spécifique des cancers du sein HER2+
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.
The Oncologist , résumé, 2010