Mismatch repair status in patients with primary operable colorectal cancer: associations with the local and systemic tumour environment

Background: Mismatch repair-deficient (dMMR) colorectal cancer (CRC) is associated with a conspicuous local immune infiltrate; however, its relationship with systemic inflammatory responses remains to be determined. The present study aims to examine the relationships and prognostic value of assessment of the local and systemic environment in the context of MMR status in patients with CRC. Methods: The relationship between MMR status, determined using immunohistochemistry, and the local inflammatory cell infiltrate, differential white cell count, neutrophil : platelet score (NPS), neutrophil : lymphocyte ratio and modified Glasgow Prognostic Score (mGPS), and cancer-specific survival was examined in 228 patients undergoing resection of stage I-III CRC. Results: Thirty-five patients (15%) had dMMR CRC. Mismatch repair deficiency was associated with a higher density of CD3(+), CD8(+) and CD45R0(+) T lymphocytes within the cancer cell nests and an elevated mGPS (mGPS2: 23% vs 9%, P = 0.007) and NPS (NPS2: 19% vs 3%, P = 0.001). CD3(+) density (P<0.001), mGPS (P = 0.01) and NPS (P = 0.042) were associated with survival independent of MMR status (P = 0.367) and stratified 5-year survival of patients with MMR-competent CRC from 94% to 67%, 83% to 46% and 78% to 60% respectively. Conclusions: Mismatch repair deficiency was associated with local and systemic environments, and in comparison with their assessment, dMMR had relatively poor prognostic value in patients with primary operable CRC. In addition to MMR status, local and systemic inflammatory responses should be assessed in these patients.