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Updated: Sep 14, 2025
Advanced Animal Model of Colorectal Metastasis in Liver: Imaging Techniques and Properties of Metastatic Clones
Published on: November 30, 2016
The colorectal liver metastasis growth pattern phenotype is not dependent on genotype
Diederik J Höppener1, Sanne M L Verheul2, Pieter M H Nierop1
1Departments of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
Background:
The histopathological growth patterns (HGPs) of colorectal cancer liver metastases broadly classify patients into two groups post-liver metastasectomy, with encapsulated HGP indicating a more favourable prognosis. The potential association between HGPs and specific mutations is poorly understood.
Methods:
Using next-generation sequencing data of 461 resected patients (104 patients with encapsulated versus 357 patients with non-encapsulated HGP), 19 putative colorectal cancer driver genes, tumour mutational burden (TMB), and microsatellite instability (MSI) or POLE mediated hypermutation were compared.
Results:
Most putative drivers, including KRAS (q = 0.89), NRAS (q = 0.98),) and BRAF (q = 0.97)), were not associated with HGP. However, mutations in B2M and PTEN were associated with a encapsulated phenotype (7% vs. 0%, q = 0.001, and 9% vs. 2%, q = 0.02, respectively). TMB was higher in encapsulated patients (median 5.8 vs. 5.1 mutations per megabase, p = 0.009). Multivariable overall survival analysis corrected for genetic and patient factors confirmed that the encapsulated phenotype was an independent prognostic factor (adjusted hazard ratio, 0.60; 95% confidence interval: 0.36-0.99). Upon stratified analysis, all identified genetic associations were equivocal between the cohorts.
Conclusions:
While an association between genetic drivers of adaptive immune responses seems probable and could explain a minority of encapsulated patients, these results primarily demonstrate that HGP phenotype is independent of the tumour genotype.
