Faculty Collaboration Database

Topoisomerase expression and amplification in solid tumours: Analysis of 24,262 patients. Eur J Cancer 2017 Sep;83:80-87

Date

07/21/2017

Pubmed ID

28728050

Pubmed Central ID

PMC5613945

DOI

10.1016/j.ejca.2017.06.019

Scopus ID

2-s2.0-85024106522 (requires institutional sign-in at Scopus site)   50 Citations

Abstract

BACKGROUND: Topoisomerase I (TOPO1) and topoisomerase IIα (TOP2A) are specific targets of multiple chemotherapy drugs. Increased expression of TOPO1 protein and amplification of the TOP2A gene have been associated with treatment response in colorectal and breast cancers, respectively. TOPO1 and TOP2A may be potential therapeutic targets in other malignancies as well.

SUMMARY OF METHODS: We analysed TOPO1 protein expression and TOP2A gene amplification in patients (n = 24,262 specimens) with diverse cancers. Since HER2 and TOP2A co-amplification have been investigated for predictive value regarding anthracycline benefit, we analysed specimens for HER2 amplification as well.

RESULTS: Overexpressed TOPO1 protein was present in 51% of the tumours. Four percent of the tumours had TOP2A amplification, with gallbladder tumours and gastroesophageal/oesophageal tumours having rates over 10%. Overall, 4903 specimens were assessed for both TOP2A and HER2 amplification; 129 (2.6%) had co-amplification. High rates (>40%) of HER2 amplification were seen in patients with TOP2A amplification in breast, ovarian, gastroesophageal/oesophageal and pancreatic cancer.

CONCLUSION: Our data indicate that increased TOPO1 expression and TOP2A amplification, as well as HER2 co-alterations, are present in multiple malignancies. The implications of these observations regarding sensitivity to chemotherapy not traditionally administered to these tumour types merits investigation.

Author List

Heestand GM, Schwaederle M, Gatalica Z, Arguello D, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antigens, Neoplasm
Biomarkers, Tumor
DNA Topoisomerases, Type I
DNA Topoisomerases, Type II
DNA-Binding Proteins
Female
Humans
Immunohistochemistry
Male
Neoplasms
Poly-ADP-Ribose Binding Proteins