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

Abstract

PurposeGenetic 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).MethodsAll 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.ResultsThere 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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (10.1245/s10434-019-07923-6) contains supplementary material, which is available to authorized users.

Omics analyses in peritoneal metastasis—utility in the management of peritoneal metastases from colorectal cancer and pseudomyxoma peritonei: a narrative review

“…Two of the studies identified CNV in large areas of the genome, with genes associated with CRC being present in gained regions of chromosome 1p (REG4 and NOTCH2) and 15q (MAP2K1, SMAD3, SMAD6 and IGF1R). Chromosomal gains in these regions (both chr 1p and 15q or in 15q alone) were associated with poor overall survival (≤2 years) following CRS-HIPEC (35). When comparing CNV in PM-CRC with other CRC locations, gains in chromosomes 5p and 12p were found to be more commonly present in PM-CRC (38).…”

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases from Colorectal Cancer—An Overview of Current Status and Future Perspectives

“…Other factors, such as advanced n stage [72], signet ring cell differentiation [26], BRAF mutation [29], and gains of chromosome 1p and 15q [74], also have negative effects on the prognosis. A recent study suggests that BRAF mutations also increase the risk of metachronous peritoneal metastasis in colon cancer patients and thereby also imply an increased risk of recurrence after CRS and HIPEC [75].…”

Delineating the intra-patient heterogeneity of molecular alterations in treatment-naïve colorectal cancer with peritoneal carcinomatosis

“…Today, the two most important factors for a successful CRS procedure is a low peritoneal carcinoma index (PCI) score and completeness of cytoreduction (CC) 11 , but there is a pressing need to identify better prognostic and predictive tools to achieve a more adequate patient selection. While several studies have characterised the molecular landscape in liver and lung metastases originating from CRC 12 – 14 , PC has been much less explored in this regard 15 . Further insight could therefore lead to improvements in the clinical management of these patients.…”