The colorectal liver metastasis growth pattern phenotype is not dependent on genotype Journal Article
| Authors: | 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.; Koerkamp, B. G.; Grünhagen, D. J.; Verhoef, C.; Primrose, J. N.; D'Angelica, M. I. |
| Article Title: | The colorectal liver metastasis growth pattern phenotype is not dependent on genotype |
| Abstract: | BackgroundThe 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.MethodsUsing 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.ResultsMost 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.ConclusionsWhile 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. |
| Keywords: | cetuximab; sensitivity; blockade; mutational landscape; systemic chemotherapy; cancer; prognosis |
| Journal Title: | British Journal of Cancer |
| ISSN: | 0007-0920 |
| Publisher: | Nature Publishing Group |
| Publication status: | Online ahead of print |
| Date Published: | 2025-01-01 |
| Online Publication Date: | 2025-01-01 |
| Language: | English |
| ACCESSION: | WOS:001534331900001 |
| DOI: | 10.1038/s41416-025-03103-4 |
| PROVIDER: | wos |
| Notes: | Article; Early Access -- Source: Wos |
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