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Open Access 01-12-2019 | Metastasis | Translational Research and Biomarkers

Gains of Chromosome 1p and 15q are Associated with Poor Survival After Cytoreductive Surgery and HIPEC for Treating Colorectal Peritoneal Metastases

Authors: Malin Enblad, MD, PhD, Wilhelm Graf, MD, PhD, Alexei Terman, MD, PhD, Pascal Pucholt, PhD, Björn Viklund, Anders Isaksson, PhD, Helgi Birgisson, MD, PhD

Published in: Annals of Surgical Oncology | Issue 13/2019

Abstract

Purpose

Genetic alterations in colorectal peritoneal metastases (PM) are largely unknown. This study was designed to analyze whole-genome copy number alterations (CNA) in colorectal PM and to identify alterations associated with prognosis after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods

All patients with PM, originating from a colorectal adenocarcinoma, who were treated with CRS and HIPEC in Uppsala Sweden, between 2004 and 2015, were included (n = 114). DNA derived from formalin-fixed paraffin-embedded (FFPE) specimens were analyzed for CNA using molecular inversion probe arrays.

Results

There were extensive but varying degrees of CNA, ranging from minimal CNA to total aneuploidy. In particular, gain of parts of chromosome 1p and major parts of 15q were associated with poor survival. A combination of gains of 1p and 15q was associated with poor survival, also after adjustment for differences in peritoneal cancer index and completeness of cytoreduction score [hazard ratio (HR) 5.96; 95% confidence interval (CI) 2.19–16.18]. These patients had a mean copy number (CN) of 3.19 compared with 2.24 in patients without gains. Complete CN analysis was performed in 53 patients. Analysis was unsuccessful for the remaining patients due to insufficient amounts of DNA and signals caused by interstitial components and normal cells. There was no difference in survival between patients with successful and unsuccessful CN analysis.

Conclusions

This study shows that gains of parts of chromosome 1p and of major parts of chromosome 15q were significantly associated with poor survival after CRS and HIPEC, which could represent future prognostic biomarkers.

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Title: Gains of Chromosome 1p and 15q are Associated with Poor Survival After Cytoreductive Surgery and HIPEC for Treating Colorectal Peritoneal Metastases
Authors: Malin Enblad, MD, PhD
Wilhelm Graf, MD, PhD
Alexei Terman, MD, PhD
Pascal Pucholt, PhD
Björn Viklund
Anders Isaksson, PhD
Helgi Birgisson, MD, PhD
Publication date: 01-12-2019
Publisher: Springer International Publishing
Keyword: Metastasis
Published in: Annals of Surgical Oncology / Issue 13/2019
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-019-07923-6

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Gains of Chromosome 1p and 15q are Associated with Poor Survival After Cytoreductive Surgery and HIPEC for Treating Colorectal Peritoneal Metastases

Abstract

Purpose

Methods

Results

Conclusions

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Abstract

Purpose

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