PMID- 21705665 OWN - NLM STAT- MEDLINE DCOM- 20120131 LR - 20211020 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 16 IP - 7 DP - 2011 TI - TOP2A amplification in the absence of that of HER-2/neu: toward individualization of chemotherapeutic practice in breast cancer. PG - 949-55 LID - 10.1634/theoncologist.2011-0071 [doi] AB - PRIMARY OBJECTIVE: To investigate the relationship between human epidermal growth factor receptor (HER)-2/neu and the gene encoding topoisomerase IIalpha (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. FAU - Glynn, Ronan W AU - Glynn RW AD - Department of Surgery, Clinical Science Institute, National University of Ireland, Galway, Ireland. FAU - Mahon, Sarah AU - Mahon S FAU - Curran, Catherine AU - Curran C FAU - Callagy, Grace AU - Callagy G FAU - Miller, Nicola AU - Miller N FAU - Kerin, Michael J AU - Kerin MJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110624 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Antigens, Neoplasm) RN - 0 (DNA-Binding Proteins) RN - 0 (Poly-ADP-Ribose Binding Proteins) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - EC 5.99.1.3 (DNA Topoisomerases, Type II) RN - EC 5.99.1.3 (TOP2A protein, human) SB - IM CIN - Oncologist. 2012;17(12):e60-1. PMID: 22821647 MH - Adult MH - Aged MH - Aged, 80 and over MH - Antigens, Neoplasm/*genetics MH - DNA Topoisomerases, Type II/*genetics MH - DNA-Binding Proteins/*genetics MH - ErbB Receptors/genetics/metabolism MH - Female MH - Gene Amplification MH - Humans MH - Immunohistochemistry MH - Middle Aged MH - Poly-ADP-Ribose Binding Proteins MH - Real-Time Polymerase Chain Reaction MH - Receptor, ErbB-2/*genetics PMC - PMC3228145 COIS- Disclosures: Ronan W. Glynn: None; Sarah Mahon: None; Catherine Curran: None; Grace Callagy: None; Nicola Miller: None; Michael J. Kerin: None. The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors or independent peer reviewers. EDAT- 2011/06/28 06:00 MHDA- 2012/02/01 06:00 PMCR- 2012/07/01 CRDT- 2011/06/28 06:00 PHST- 2011/06/28 06:00 [entrez] PHST- 2011/06/28 06:00 [pubmed] PHST- 2012/02/01 06:00 [medline] PHST- 2012/07/01 00:00 [pmc-release] AID - theoncologist.2011-0071 [pii] AID - 3707398 [pii] AID - 10.1634/theoncologist.2011-0071 [doi] PST - ppublish SO - Oncologist. 2011;16(7):949-55. doi: 10.1634/theoncologist.2011-0071. Epub 2011 Jun 24.