TOP2A gene copy number change in breast cancer

• Published in: Journal of clinical pathology Vol. 67; no. 5; p. 420
• Main Authors: Engstrøm, M J, Ytterhus, B, Vatten, L J, Opdahl, S, Bofin, A M
• Format: Journal Article
• Language: English
• Published: England 01-05-2014
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm - genetics; Biomarkers, Tumor - chemistry; Biomarkers, Tumor - genetics; Breast Neoplasms - chemistry; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Chromosomes, Human, Pair 17; DNA Copy Number Variations; DNA Topoisomerases, Type II - genetics; DNA-Binding Proteins - genetics; Female; Gene Amplification; Gene Deletion; Gene Dosage; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Hybridization; Kaplan-Meier Estimate; Middle Aged; Poly-ADP-Ribose Binding Proteins; Predictive Value of Tests; Prognosis; Receptor, ErbB-2 - genetics
• ISSN: 1472-4146
• DOI: 10.1136/jclinpath-2013-202052

The clinical significance of TOP2A as a prognostic marker has not been clarified. The aims of this study were to investigate the frequency of TOP2A copy number change; to correlate TOP2A with HER2 status, hormone receptor (HR) status and molecular subtype, and further to explore differences in breast cancer-specific survival according to TOP2A and HER2.
In this study, TOP2A, HER2 and chromosome 17 copy number were assessed in 670 cases of breast cancer using in situ hybridisation techniques. Gene to chromosome ratios ≥2 were classified as amplification. TOP2A deletion (gene to chromosome ratio ≤0.8) or monosomy (only one signal for both gene and chromosome in more than 75% of nuclei) were classified as gene loss.
A strong association between TOP2A change and HR and HER2 status was found. During the first 5 years after diagnosis, the risk of death from breast cancer was significantly higher for cases with HER2 amplification irrespective of TOP2A status.
TOP2A copy number change was strongly associated with HR and HER2 status and as a prognostic marker TOP2A is probably of limited value.