title: The expression and prognostic impact of CXC-chemokines in stage II and III colorectal cancer epithelial and stromal tissue.
abstract: BACKGROUND
  The CXC-chemokine expression is linked with colorectal cancer (CRC) progression but their significance in resected CRC is unclear. We explored the prognostic impact of such expression in stage II and III CRC.
  
  
  METHODS
  Tissue microarrays were constructed from stage II and III CRC biopsies (n=254), and the expression of CXCL1 and CXCL8, and their receptors CXCR1 and CXCR2, in malignant and adjacent normal tissue was graded by immunohistochemistry and was correlated with prognostic factors.
  
  
  RESULTS
  Expression of CXCL1, CXCR1 and CXCR2 was elevated in tumour epithelium relative to normal adjacent tissue (P<0.001). CXCL8 expression was detectable in the peritumoural inflammatory infiltrate. There was no overall association between CXCL1, CXCR1 or CXCR2 expression and prognostic endpoints; however, univariate subgroup survival analysis demonstrated an inverse association between CXCL1 and recurrence-free survival (RFS) in stage III patients (P=0.041). The CXCL8 positivity in the tumour infiltrate, however, correlated with earlier disease stage (P<0.001) and improved relapse-free survival across the cohort (P<0.001). Disease stage (P<0.001) and tumour infiltrate CXCL8 positivity (P=0.007) were associated with enhanced RFS in multivariate Cox regression analysis.
  
  
  CONCLUSIONS
  Autocrine CXC-chemokine signalling may have adverse prognostic effects in early CRC. Conversely, CXCL8 positivity within the immune infiltrate may have good prognostic significance.
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland.
authors.forename: O
authors.initials: O
authors.lastname: Oladipo
authors.forename: S
authors.initials: S
authors.lastname: Conlon
authors.forename: A
authors.initials: A
authors.lastname: O'Grady
authors.forename: C
authors.initials: C
authors.lastname: Purcell
authors.forename: C
authors.initials: C
authors.lastname: Wilson
authors.forename: P J
authors.initials: PJ
authors.lastname: Maxwell
authors.forename: P G
authors.initials: PG
authors.lastname: Johnston
authors.forename: M
authors.initials: M
authors.lastname: Stevenson
authors.forename: E W
authors.initials: EW
authors.lastname: Kay
authors.forename: R H
authors.initials: RH
authors.lastname: Wilson
authors.forename: D J J
authors.initials: DJ
authors.lastname: Waugh
mesh_terms: D019743:Chemokines, CXC / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D017154:Stromal Cells / Q000378:metabolism*
chemical_list: D019743:Chemokines, CXC; D016209:Interleukin-8