Associations of non-pedunculated T1 colorectal adenocarcinoma outcome with consensus molecular subtypes, immunoscore, and microsatellite status: a multicenter case-cohort study
Open accessAbstract
Advanced colorectal cancer (CRC) consensus molecular subtype 4 (CMS4) or CRC with a low immunoscore is associated with shorter survival times. Non-metastatic CRC with microsatellite instability (MSI) is associated with a lower risk of recurrence. We evaluated outcome (lymph node metastases [LNM] or cancer recurrence) in these tumor subtypes in patients with surgically-removed non-pedunculated T1 CRC by performing a multicenter case-cohort study. We included all patients in 13 hospitals in the Netherlands from 2000-2014 (n = 651). We randomly selected a subgroup of patients (n = 223) and all patients with LNM or recurrence (n = 63), and median follow-up of 44 months. We centrally reviewed tumor-slides, and constructed and immunostained tissue microarrays determining MSI, CMS (MSI/CMS1, CMS2/3, or CMS4), and immunoscore (I-low/I-high). We used weighted Cox proportional hazard models to evaluate the association of MSI, CMS, and immunoscore with LNM or recurrence, adjusting for conventional histologic risk factors. In the randomly selected subgroup of patients, 7.1% of tumors were MSI/CMS1, 91.0% CMS2/3, 1.8% CMS4, and 25% I-low. In the case-cohort, patients with CMS4 tumors had an increased risk for LNM or recurrence compared with patients with tumors of other CMSs (adjusted hazard ratio [HR], 3.97; 95% CI, 1.12-14.06; P = 0.03). Albeit not significant, tumors with MSI had a lower risk for LNM or recurrence than other tumor subtypes (adjusted HR, 0.52; 95% CI, 0.12-2.30; P = 0.39), whereas tumors with a low immunoscore had an increased risk for LNM or recurrence (adjusted HR, 1.30; 95% CI, 0.68-2.48; P = 0.43). In conclusion, in a case-cohort study of patients with non-pedunculated T1 CRC, MSI, and immunoscore were not significantly associated with adverse outcome after surgery. CMS4 substantially increased the risk of adverse outcome. However, CMS4 is rare in T1 CRCs, limiting its value for determining the risk in patients.
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CMS4 colorectal cancer is consistently associated with a dismal outcome, including at early stage.
“CMS4 colorectal cancer is consistently associated with a dismal outcome (1, 26), including at early stage (27).”
From Clinical Challenges of Consensus Molecular Subtype CMS4 Colon Cancer in the Era of Precision Medicine (2024) · cites this paper as [27]
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- Authors
- Haasnoot, K. J. C., Backes, Y., Moons, L. M. G., Kranenburg, O., Trinh, A., Vermeulen, L., Noë, M., Tuynman, J. B., van Lent, A. U. G., van Ginneken, R., Seldenrijk, C. A., Raicu, M. G., Trumpi, K., Ubink, I., Milne, A. N., Boonstra, J. J., Groen, J. N., Schwartz, M. P., Wolfhagen, F. H. J., Geesing, J. M. J., ter Borg, F., Brosens, L. A. A., van Bergeijk, J., Spanier, B. W. M., de Vos tot Nederveen Cappel, W. H., Kessels, K., Seerden, T. C. J., Vleggaar, F. P., Offerhaus, G. J. A., Siersema, P. D., Elias, S. G., & Laclé, M. M.
- Affiliations
- University Medical Center Utrecht (NL)
- Harvard University (US)
- Oncode Institute (NL)
- Johns Hopkins University (US)
- Amsterdam University Medical Centers (NL)
- St. Antonius Ziekenhuis (NL)
- Leiden University Medical Center (NL)
- Meander Medisch Centrum (NL)
- Albert Schweitzer Ziekenhuis (NL)
- Diakonessenhuis hospital (NL)
- Rijnstate Hospital (NL)
- Amphia Ziekenhuis (NL)
- Radboud University Medical Center (NL)
- Corresponding author
- Laclé, Miangela M.
- ORCID
- Haasnoot, Krijn J.C.
- Backes, Yara
- Moons, Leon M.G.
- Kranenburg, Onno
- Trinh, Anne
- Vermeulen, Louis
- Noë, Michaël
- Tuynman, Jurriaan B.
- Raicu, Mihaela G.
- Trumpi, Kari
- Ubink, Inge
- Boonstra, Jurjen J.
- Schwartz, Matthijs P.
- Wolfhagen, Frank H.J.
- Brosens, Lodewijk A.A.
- Kessels, Koen
- Vleggaar, Frank P.
- Offerhaus, G. Johan A.
- Siersema, Peter D.
- Elias, Sjoerd G.
- Laclé, Miangela M.
- Venue
- Modern Pathology
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 33
- Issue
- 12
- Pages
- 2626-2636
- ISSN
- 0893-3952 (ISSN-L)
- OpenAlex
- W3037259777
- Cited by
- 30
- References
- 40
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 2
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Modern Pathology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Maag Lever Darm Stichting (MG/2015-040)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Keywords
- colorectal adenocarcinoma, T1 colorectal cancer, consensus molecular subtypes, CMS4, microsatellite instability, immune score, lymph node metastasis, tumor recurrence, surgical resection, prognostic factors, tumor microenvironment, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, tumor-infiltrating neutrophils
- MeSH terms
- Adenocarcinoma, Aged, Female, Humans, Immunohistochemistry, Male, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Netherlands, Phenotype, Predictive Value of Tests, Time Factors, Biomarkers, Tumor, Colorectal Neoplasms, Case-Control Studies, Treatment Outcome, Genetic Predisposition to Disease, DNA Repair Enzymes, Tissue Array Analysis, Microsatellite Instability
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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