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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

Topoisomerase I copy number alterations as biomarker for irinotecan efficacy in metastatic colorectal cancer

Authors: Jesper Andreas Palshof, Estrid Vilma Solyom Høgdall, Tim Svenstrup Poulsen, Dorte Linnemann, Benny Vittrup Jensen, Per Pfeiffer, Line Schmidt Tarpgaard, Nils Brünner, Jan Stenvang, Mette Yilmaz, Dorte Lisbet Nielsen

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

No biomarker exists to guide the optimal choice of chemotherapy for patients with metastatic colorectal cancer. We examined the copy numbers (CN) of topoisomerase I (TOP1) as well as the ratios of TOP1/CEN-20 and TOP1/CEN-2 as biomarkers for irinotecan efficacy in patients with metastatic colorectal cancer.

Methods

From a national cohort, we identified 163 patients treated every third week with irinotecan 350 mg/m2 as second-line therapy. Among these 108 were eligible for analyses and thus entered the study. Primary tumors samples were collected and tissue microarray (TMA) blocks were produced. FISH analysis was performed using two probe-mixes: TOP1/CEN-20 and TOP1/CEN-2. Only samples harboring all three signals (TOP1, CEN-20 and CEN-2) using FISH were included in the analyses.

Results

In the TOP1/CEN-20 probe-mix the median TOP1- and CEN-20 CN were 4.46 (range: 1.5–9.5) and 2.00 (range: 0.55–4.55), respectively. The median TOP1- and CEN-2 CN in the TOP1/CEN-2 probe-mix, were 4.57 (range: 1.82–10.43) and 1.98 (range: 1.22–6.14), respectively. The median TOP1/CEN-20 ratio and TOP1/CEN-2 ratio were 1.25 (range: 0.92–2.90) and 2.05 (range: 1.00–6.00), respectively. None of the markers TOP1 CN, TOP1/CEN-20-ratio or TOP1/CEN-2-ratio were associated with progression free survival, overall survival or baseline characteristics. Yet, we observed a borderline association for a stepwise increase of the TOP1 CN in relation to objective response as hazard ratio were 1.35 (95% CI 0.96–1.90; p = 0.081).

Conclusions

We verified a borderline significant association between increasing TOP1 CN and objective response as previously reported. Applying the probes representing CEN-20 and CEN-2, in order to investigate the ratios of TOP1/CEN-20 and TOP1/CEN-2 provided no further information in search of a biomarker driven patient stratification. Other biomarkers to be paired with TOP1 CN are therefore highly warranted.
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Metadata
Title
Topoisomerase I copy number alterations as biomarker for irinotecan efficacy in metastatic colorectal cancer
Authors
Jesper Andreas Palshof
Estrid Vilma Solyom Høgdall
Tim Svenstrup Poulsen
Dorte Linnemann
Benny Vittrup Jensen
Per Pfeiffer
Line Schmidt Tarpgaard
Nils Brünner
Jan Stenvang
Mette Yilmaz
Dorte Lisbet Nielsen
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-3001-y

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