title: CD8+ lymphocytes/ tumour-budding index: an independent prognostic factor representing a 'pro-/anti-tumour' approach to tumour host interaction in colorectal cancer.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Pathology, University of Basel, Basel, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Lugli
authors.forename: E
authors.initials: E
authors.lastname: Karamitopoulou
authors.forename: I
authors.initials: I
authors.lastname: Panayiotides
authors.forename: P
authors.initials: P
authors.lastname: Karakitsos
authors.forename: G
authors.initials: G
authors.lastname: Rallis
authors.forename: G
authors.initials: G
authors.lastname: Peros
authors.forename: G
authors.initials: G
authors.lastname: Iezzi
authors.forename: G
authors.initials: G
authors.lastname: Spagnoli
authors.forename: M
authors.initials: M
authors.lastname: Bihl
authors.forename: L
authors.initials: L
authors.lastname: Terracciano
authors.forename: I
authors.initials: I
authors.lastname: Zlobec
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053842:Microsatellite Instability; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D046888:Tissue Array Analysis; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins