The expression and prognostic impact of CXC-chemokines in stage II and III colorectal cancer epithelial and stromal tissue

BACKGROUND: The CXC-chemokine expression is linked with coloredal cancer (CRC) progression but their signifcance 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 CXCLI and CXCL8, and their receptors CXCRI and CXCR2, in malignant and adjacent normal tissue was graded by immunohistochemistry and was correlated with prognostic factors. RESULTS: Expression of CXCLI, CXCRI 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 CXCLI, CXCRI or CXCR2 expression and prognostic endpoints; however, univariate subgroup survival analysis demonstrated an inverse association between CXCLI and recurrence-free survival (RFS) in stage III patients (P=0.041). The CXCL8 positivity in the tumour infltrate, however, correlated with earlier disease stage (P<0.00I) and improved relapse-free survival across the cohort (P<0.00I). Disease stage (P<0.00I) and tumour infiltrate CXCL8 positivity (P=0.007) were associated with enhanced RFS in multivariate Cox regression analysis. CONCLUSION: Autocrine CXC-chemokine signalling may have adverse prognostic effects in early CRC. Conversely, CXCL8 positivity within the immune infltrate may have good prognostic signifcance.