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

Abstract

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.

Prognostic significance of nomograms integrating IL‐37 expression, neutrophil level, and MMR status in patients with colorectal cancer

“…An unexpected finding was an association between dMMR status and an elevated CD66b + TAN level. Of interest, consistent with recent work by Park et al6, dMMR status was associated with an elevated circulating neutrophil count.…”

“…A large multicenter study supports the use of adjuvant chemotherapy with fluoropyrimidine plus oxaliplatin for stage III‐dMMR colon cancer 34. The extent of neutrophil infiltration in human CRC has been shown to differ based on MMR status 6, 33…”

“…Although outcome and the need for adjuvant chemotherapy are routinely determined using the International Union Against Cancer (UICC) Tumor‐Node‐Metastasis (TNM) staging system, large variations in prognosis have been showed among patients with disease of the same stage and undergoing similar treatment 2, 3, 4. In fact, other tumor‐associated characteristics, such as those intrinsic to tumor cells and those related to the interactions of cancer cells with microenvironmental stimuli, might similarly influence CRC prognosis and be applied to evaluate the necessity of further treatment 5, 6…”

A novel tumor‐based epithelial‐to‐mesenchymal transition score that associates with prognosis and metastasis in patients with Stage II/III colorectal cancer

“…Ki67 was already available for this cohort using a threshold of 50%. MMR status was assessed as previously described . Patients were followed up for at least 5 years, and date and cause of death were crosschecked with electronic case records.…”

Colorectal cancer subtypes: Translation to routine clinical pathology

“…TILs at both the invasive margin of the tumour and within the cancer cell nests slow tumour growth and invasion and are associated with a better patient prognosis [27]. 5yr survival rates for cytotoxic CD8+ T-lymphocytes at both locations are 37.3% when both low, 61.1% when one high and 73.8% when both high, therefore TILS would appear to be a stronger prognostic factor than MSI for CMS1 [33,34].…”