University of Oulu

Wirta, E.-V., Seppälä, T., Friman, M., Väyrynen, J., Ahtiainen, M., Kautiainen, H., Kuopio, T., Kellokumpu, I., Mecklin, J.-P. and Böhm, J. (2017), Immunoscore in mismatch repair-proficient and -deficient colon cancer. J Path: Clin Res, 3: 203–213. doi:10.1002/cjp2.71

Immunoscore in mismatch repair-proficient and -deficient colon cancer

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Author: Wirta, Erkki-Ville1; Seppälä, Toni2; Friman, Marjukka3;
Organizations: 1Department of Surgery, Central Finland Central Hospital
2Department of Surgery, Helsinki University Central Hospital
3Department of Pathology, Central Finland Central Hospital
4Department of Pathology, University of Oulu
5Department of Education and Research, Central Finland Central Hospital, Jyväskylä and University of Eastern Finland, Kuopio
6Department of General Practice, Unit of Primary Health Care, Helsinki University Central Hospital, University of Helsinki
7Unit of Primary Health Care, Kuopio University Hospital
8Department of Biological and Environmental Science, University of Jyväskylä
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
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Language: English
Published: John Wiley & Sons, 2017
Publish Date: 2017-10-06


The aim of this study was to investigate immune response and its prognostic significance in colon carcinomas using the previously described Immunoscore (IS). A population-based series of 779 colorectal cancers, operated on between 2000 and 2010, were classified according to tumour, node, metastasis (TNM) status, mismatch repair (MMR), and BRAF mutation status. Rectal cancer cases (n = 203) were excluded as a high proportion of these patients received preoperative neoadjuvant chemoradiotherapy. Tissue microarray (TMA) samples collected from the tumour centre and invasive front were immunostained for CD3 and CD8. Lymphocytes were then digitally calculated to categorize IS from grade 0 to 4. Samples adequate for IS were available from 510 tumours. IS was significantly associated with AJCC/UICC stage, T stage, lymph node and distant metastases, perineural and lymphovascular invasion, MMR status, and BRAF mutation status. For IS0, IS1, IS2, IS3 and IS4, respectively, the 5-year disease-free survival (DFS) rates were 59, 68, 78, 83 and 94% (p < 0.001); 5-year disease-specific survival (DSS) rates were 47, 55, 75, 80, and 89% (p < 0.001); and 5-year overall survival (OS) rates were 40, 44, 66, 61, and 76% (p < 0.001). IS was also prognostic for DFS, DSS, and OS within subsets of microsatellite-stable (MSS) and microsatellite-instable (MSI) disease. Multivariable analysis showed that IS, AJCC/UICC stage, lymphovascular invasion, and lymph node ratio in AJCC/UICC stage III disease were independent prognostic factors for DFS, DSS, and OS. Age was an independent prognostic factor for DSS and OS. Gender and BRAF mutation were independent prognostic factors for OS. In conclusion, IS differentiated patients with poor versus improved prognosis in MSS and MSI disease and across AJCC/UICC stages. IS, AJCC/UICC stage, lymphovascular invasion, and lymph node ratio in AJCC/UICC stage III disease were independent prognostic factors for DFS, DSS, and OS.

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Series: Journal of pathology. Clinical research
ISSN: 2056-4538
ISSN-E: 2056-4538
ISSN-L: 2056-4538
Volume: 3
Issue: 3
Pages: 203 - 213
DOI: 10.1002/cjp2.71
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This study received funding from the Finnish Cancer Foundation, Jane and Aatos Erkko Foundation, the State Research Funding (Kuopio University Hospital Research Center) and the Finnish Medical Foundation.
Copyright information: © 2017 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.