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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

Malin Enblad MD, PhD, Wilhelm Graf MD, PhD, Alexei Terman MD, PhD, Pascal Pucholt PhD, Björn Viklund, Anders Isaksson PhD, Helgi Birgisson MD, PhD
Translational Research and Biomarkers
Volume 26, Issue 13 / December , 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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