CD8+ lymphocytes/ tumour-budding index: an independent prognostic factor representing a 'pro-/anti-tumour' approach to tumour host interaction in colorectal cancer

Br J Cancer. 2009 Oct 20;101(8):1382-92. doi: 10.1038/sj.bjc.6605318. Epub 2009 Sep 15.


Background: The tumour-host interaction at the invasive front of colorectal cancer, including the epithelial-mesenchymal transition and its hallmark 'tumour budding', is an important area of investigation in terms of prognosis. The aim of this study was to determine the prognostic impact of a 'pro-/anti-tumour' approach defined by an established 'pro-tumour' (tumour budding) and host-related 'anti-tumour' factor of the adaptive immunological microenvironment (CD8+ lymphocytes).

Methods: Double immunostaining for CK22/CD8 on whole tissue sections (n=279; Cohort 1) and immunohistochemistry for CD8+ using tissue microarrays (n=191; Cohort 2) was carried out. Tumour buds, CD8+ and CD8+ T-lymphocytes : tumour buds indices were evaluated per high-power field.

Results: In Cohort 1, a low-CD8+/ buds index was associated with lymph node metastasis (P<0.001), vascular invasion (P=0.009), worse survival in univariate (P<0.001) and multivariable (P<0.001) analysis, and furthermore in lymph node-negative patients (P=0.002). In Cohort 2, the CD8+/ buds index was associated with T stage (P<0.001), N stage (P=0.041), vascular invasion (P=0.005) and survival in patients with TNM stage II (P=0.019), stage III (P=0.004), and adjuvantly untreated (P=0.009) and treated patients (P<0.001).

Conclusion: The CD8+ lymphocyte : tumour-budding index is an independent prognostic factor in colorectal cancer and a promising approach for a future prognostic score for patients with this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Humans
  • Microsatellite Instability
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Tissue Array Analysis
  • ras Proteins / genetics


  • KRAS protein, human
  • Proto-Oncogene Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins