Chemokine receptor CXCR2 and plasminogen activator inhibitor-1 expression in colorectal adenocarcinoma are associated with prognostic features.

purposeChemokine receptor CXCR2 and plasminogen activator inhibitor-1 (PAI-1) are incipient biomarkers across various cancers. Despite their seemingly antithetical effects in the immune microenvironment, CXCR2 and PAI-1 have yet to be explored in tandem in colorectal adenocarcinoma (CRC). We compared their peritumoral expression by immunohistochemistry (IHC) to prognostic features in CRC, in both treated and untreated settings.

methodsCXCR2 and PAI-1 IHC were performed on representative sections from 192 untreated and 48 treated CRC resection specimens. The extent of peritumoral inflammation on H&E (score 0-3), CXCR2 staining in peritumoral inflammatory cells (score 0-3), and PAI-1 staining in stroma (high vs. low) and tumor (positive vs. negative) were compared to each other and to clinicopathologic features. Survival analyses used Kaplan-Meier estimation.

resultsIn both untreated and treated CRC, increased peritumoral inflammation was associated with lower pT/pN stage, fewer positive lymph nodes, and higher CXCR2 scores. In untreated CRC, higher CXCR2 scores correlated with absence of tumor deposits, lower clinical stage, and fewer positive lymph nodes. High stromal PAI-1 correlated with higher tumor bud count/score and positive lymph nodes. In treated CRC, high stromal PAI-1 was associated with higher CXCR2 scores, a trend also seen in a subset of untreated tumors with favorable prognostic features. Patients with greater inflammation scores showed longer recurrence-free survival.

conclusionsCXCR2 expression is associated with favorable prognostic features regardless of prior therapy. In untreated CRC, stromal PAI-1 expression is associated with less favorable features. These findings are notable, as anti-PAI-1 small molecule inhibitors are under investigation.