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Background <p>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.</p> Methods <p>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 <i>POLE</i> mediated hypermutation were compared.</p> Results <p>Most putative drivers, including <i>KRAS</i> (<i>q</i> = 0.89), <i>NRAS</i> (<i>q</i> = 0.98),) and <i>BRAF</i> (<i>q</i> = 0.97)), were not associated with HGP. However, mutations in <i>B2M</i> and <i>PTEN</i> were associated with a encapsulated phenotype (7% vs. 0%, <i>q</i> = 0.001, and 9% vs. 2%, <i>q</i> = 0.02, respectively). TMB was higher in encapsulated patients (median 5.8 vs. 5.1 mutations per megabase, <i>p</i> = 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.</p> Conclusions <p>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.</p>

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The colorectal liver metastasis growth pattern phenotype is not dependent on genotype

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月23日

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  • Diederik J. Höppener,
  • Sanne M. L. Verheul,
  • Pieter M. H. Nierop,
  • Florian E. Buisman,
  • Boris Galjart,
  • Saskia M. Wilting,
  • Siân A. Pugh,
  • Susan D. Richman,
  • Vinod P. Balachandran,
  • William R. Jarnagin,
  • T. Peter Kingham,
  • Peter B. Vermeulen,
  • Jinru Shia,
  • Philip Quirke,
  • John A. Bridgewater,
  • Timothy S. Maughan,
  • Bas Groot Koerkamp,
  • Dirk J. Grünhagen,
  • Cornelis Verhoef,
  • John N. Primrose,
  • Michael I. D’Angelica,
  • Philip Quirke

摘要

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.