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

Höppener, DJ; Verheul, SML; Nierop, PMH; Buisman, FE; Galjart, B; Wilting, SM; Pugh, SA; Richman, SD; Balachandran, VP; Jarnagin, WR; Kingham, TP; Vermeulen, PB; Shia, J; Quirke, P; Bridgewater, JA; Maughan, TS; Groot Koerkamp, B; Grünhagen, DJ; Verhoef, C; Primrose, JN; D’Angelica, MI

Journal article

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

Alternative title:: Cellular and Molecular Biology

Abstract:: 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.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Höppener, D. J., Verheul, S. M. L., Nierop, P. M. H., Buisman, F. E., Galjart, B., Wilting, S. M., Pugh, S. A., Richman, S. D., Balachandran, V. P., Jarnagin, W. R., Kingham, T. P., Vermeulen, P. B., Shia, J., Quirke, P., Bridgewater, J. A., Maughan, T. S., Groot Koerkamp, B., Grünhagen, D. J., Verhoef, C., … D’Angelica, M. I. (2025). The colorectal liver metastasis growth pattern phenotype is not dependent on genotype. British Journal of Cancer, 133(7), 945–955.

MLA Style

Höppener, DJ, et al. “The Colorectal Liver Metastasis Growth Pattern Phenotype Is Not Dependent on Genotype.” British Journal of Cancer, vol. 133, no. 7, 2025, pp. 945–55.

Chicago Style

Höppener, DJ, SML Verheul, PMH Nierop, et al. 2025. “The Colorectal Liver Metastasis Growth Pattern Phenotype Is Not Dependent on Genotype.” British Journal of Cancer 133 (7): 945–55.
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