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

Park, J. H. , Powell, A. G., Roxburgh, C. S.D. , Horgan, P. G. , McMillan, D. c. and Edwards, J. (2016) Mismatch repair status in patients with primary operable colorectal cancer: associations with the local and systemic tumour environment. British Journal of Cancer, 114, pp. 562-570. (doi: 10.1038/bjc.2016.17) (PMID:26859693)

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 (NLR) and modified Glasgow Prognostic Score (mGPS), and cancer-specific survival was examined in 228 patients undergoing resection of stage I-III CRC. RESULTS: 35 patients (15%) had dMMR CRC. dMMR was associated with a higher density of CD3+, CD8+, 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 five-year survival of patients with MMR competent CRC from 94% to 67%, 83% to 46% and 78% to 60% respectively. CONCLUSION: MMR deficiency was associated with local and systemic environments, and compared 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Park, Mr James and Horgan, Professor Paul and Roxburgh, Professor Campbell and Edwards, Professor Joanne and Powell, Dr Arfon and McMillan, Professor Donald
• Authors: Park, J. H., Powell, A. G., Roxburgh, C. S.D., Horgan, P. G., McMillan, D. c., and Edwards, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: British Journal of Cancer
• Publisher: Cancer Research UK
• ISSN: 0007-0920
• ISSN (Online): 1532-1827