Tumour-infiltrating CD68+ and CD57+ cells predict patient outcome in stage II-III colorectal cancer

Br J Cancer. 2013 Aug 20;109(4):1013-22. doi: 10.1038/bjc.2013.362. Epub 2013 Jul 18.

Abstract

Background: The aim of our study was to evaluate the prognostic role of immunological microenvironnement in stage II-III CRC patients.

Methods: We constructed a tissue microarray from 196 consecutive patients with stage II-III CRC and compared CD3, CD4, CD8, CD57, CD68, CXCL9/MIG, CXCL13, and PPARγ immunoreactivity in tumour samples and their matched non-tumour tissue. We assessed their association with relapse-free survival (RFS; primary endpoint) and overall survival (OS) in multivariate Cox models.

Results: Low densities of CD57+ and CD68+ tumour-infiltrating cells (TIC) independently predicted worse outcomes. A prognostic score combining CD57 (+, > vs -, ≤2 cells per spot) and CD68 (+, >0 vs -, =0 cells per spot) TIC density discriminated CRC patients at low (CD68+/CD57+), intermediate (CD68+/CD57-), or high (CD68-/CD57-) risk, with hazard ratios for the intermediate-risk and high-risk groups of 2.7 (95% confidence interval (CI): 1.3-5.8) and 9.0 (3.2-25.4) for RFS, and 2.5 (1.2-5.1) and 10.6 (3.8-29.2) for OS, respectively, as compared with the low-risk group. Corresponding 5-year survival rates (95% CI) in the low-, moderate- and high-risk groups were 84% (71-91), 65% (54-74), and 12% (2-47), respectively, for RFS, and 91% (80-96), 76% (66-84), and 25% (7-59), respectively, for OS.

Conclusion: Tumour CD57+ and CD68+ TIC density assessment independently predicts survival in patients with stage II-III CRC. If validated, our score based on a quick, inexpensive, and well-established method such as point counting on diagnostic tissue sections could be used routinely as a prognostic tool in CRC patients.

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / immunology*
  • Antigens, Differentiation, Myelomonocytic / immunology*
  • Biomarkers
  • CD3 Complex / immunology
  • CD4 Antigens / immunology
  • CD57 Antigens / immunology*
  • CD8 Antigens / immunology
  • Cell Count
  • Chemokine CXCL13 / immunology
  • Chemokine CXCL9 / immunology
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Macrophages / immunology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • PPAR gamma / immunology
  • Prognosis
  • Proportional Hazards Models

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD3 Complex
  • CD4 Antigens
  • CD57 Antigens
  • CD68 antigen, human
  • CD8 Antigens
  • CXCL13 protein, human
  • CXCL9 protein, human
  • Chemokine CXCL13
  • Chemokine CXCL9
  • PPAR gamma