An integrated analysis of lymphocytic reaction, tumour molecular characteristics and patient survival in colorectal cancer

Br J Cancer. 2020 Apr;122(9):1367-1377. doi: 10.1038/s41416-020-0780-3. Epub 2020 Mar 11.


Background: Histological lymphocytic reaction is regarded as an independent prognostic marker in colorectal cancer. Considering the lack of adequate statistical power, adjustment for selection bias and comprehensive tumour molecular data in most previous studies, we investigated the strengths of the prognostic associations of lymphocytic reaction in colorectal carcinoma by utilising an integrative database of two prospective cohort studies.

Methods: We examined Crohn's-like reaction, intratumoural periglandular reaction, peritumoural reaction and tumour-infiltrating lymphocytes in 1465 colorectal carcinoma cases. Using covariate data of 4420 colorectal cancer cases in total, inverse probability-weighted Cox proportional hazard regression model was used to control for selection bias (due to tissue availability) and potential confounders, including stage, MSI status, LINE-1 methylation, PTGS2 and CTNNB1 expression, KRAS, BRAF and PIK3CA mutations, and tumour neoantigen load.

Results: Higher levels of each lymphocytic reaction component were associated with better colorectal cancer-specific survival (Ptrend < 0.002). Compared with cases with negative/low intratumoural periglandular reaction, multivariable-adjusted HRs were 0.55 (95% CI, 0.42-0.71) in cases with intermediate reaction and 0.20 (95% CI, 0.12-0.35) in cases with high reaction. These relationships were consistent in strata of MSI status or neoantigen loads (Pinteraction > 0.2).

Conclusions: The four lymphocytic reaction components are prognostic biomarkers in colorectal carcinoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Cyclooxygenase 2 / genetics
  • DNA Methylation / genetics*
  • Female
  • Humans
  • Long Interspersed Nucleotide Elements / genetics
  • Lymphocyte Count
  • Lymphocytes / pathology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • beta Catenin / genetics


  • Biomarkers, Tumor
  • CTNNB1 protein, human
  • KRAS protein, human
  • beta Catenin
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)