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Histological 'phenotypic subtypes' that classify patients into four groups (immune, canonical, latent and stromal) have previously been demonstrated to stratify survival in a stage I-III colorectal cancer (CRC) pilot cohort. However, clinical utility has not yet been validated. Therefore, this study assessed prognostic value of these subtypes in additional patient cohorts along with associations with risk of recurrence and response to chemotherapy. Two independent stage I-III CRC patient cohorts (internal and external cohort) were utilised to investigate phenotypic subtypes. The primary endpoint was disease-free survival (DFS) and the secondary endpoint was recurrence risk (RR). Stage II-III patients, from the SCOT adjuvant chemotherapy trial, were utilised to further validate prognostic value and for exploratory analysis assessing associations with adjuvant chemotherapy. In an 893-patient internal cohort, phenotypic subtype independently associated with DFS (p = 0.025) and this was attenuated in stage III patients (p = 0.020). Phenotypic subtype also independently associated with RR (p interaction = 0.011). Phenotypic subtype independently associated with DFS in stage III patients receiving FOLFOX (p = 0.028). Furthermore, the immune subtype significantly associated with better response to FOLFOX compared to CAPOX adjuvant chemotherapy in stage III patients (p = 0.013). In conclusion, histological phenotypic subtypes are an effective prognostic classification in patients with stage III CRC that associates with risk of recurrence and response to FOLFOX adjuvant chemotherapy.

Original publication




Journal article


The journal of pathology. Clinical research

Publication Date





283 - 296


School of Medicine, University of Glasgow, Glasgow, UK.


Humans, Colorectal Neoplasms, Neoplasm Recurrence, Local, Organoplatinum Compounds, Fluorouracil, Leucovorin, Antineoplastic Combined Chemotherapy Protocols, Neoplasm Staging, Disease-Free Survival, Chemotherapy, Adjuvant, Risk Assessment, Risk Factors, Prospective Studies, Reproducibility of Results, Predictive Value of Tests, Phenotype, Time Factors, Aged, Middle Aged, Female, Male