Immunoscore in Mismatch Repair-Proficient and -Deficient Colon Cancer
Wirta, E.-V., Seppälä, T., Friman, M., Väyrynen, J., Ahtiainen, M., Kautiainen, H., Kuopio, T., Kellokumpu, I., Mecklin, J.-P., & Böhm, J. (2017). Immunoscore in Mismatch Repair-Proficient and -Deficient Colon Cancer. Journal of Pathology, 3(3), 203-213. https://doi.org/10.1002/cjp2.71
Published inJournal of Pathology
© 2017 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License.
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 5 203) 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. ...
Publication in research information system
MetadataShow full item record
Except where otherwise noted, this item's license is described as © 2017 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License.
Showing items with similar title or keywords.
Molecular Basis of Mismatch Repair Protein Deficiency in Tumors from Lynch Suspected Cases with Negative Germline Test Results Olkinuora, Alisa; Gylling, Annette; Almusa, Henrikki; Eldfors, Samuli; Lepistö, Anna; Mecklin, Jukka-Pekka; Nieminen, Taina Tuulikki; Peltomäki, Päivi (MDPI AG, 2020)Some 10–50% of Lynch-suspected cases with abnormal immunohistochemical (IHC) staining remain without any identifiable germline mutation of DNA mismatch repair (MMR) genes. MMR proteins form heterodimeric complexes, giving ...
DNA methylation changes and somatic mutations as tumorigenic events in Lynch syndrome-associated adenomas retaining mismatch repair protein expression Mäki-Nevala, Satu; Valo, Satu; Ristimäki, Ari; Sarhadi, Virinder; Knuutila, Sakari; Nyström, Minna; Renkonen-Sinisalo, Laura; Lepistö, Anna; Mecklin, Jukka-Pekka; Peltomäki, Päivi (Elsevier BV, 2019)Background DNA mismatch repair (MMR) defects are a major factor in colorectal tumorigenesis in Lynch syndrome (LS) and 15% of sporadic cases. Some adenomas from carriers of inherited MMR gene mutations have intact MMR ...
Immune Contexture of MMR-Proficient Primary Colorectal Cancer and Matched Liver and Lung Metastases Ahtiainen, Maarit; Elomaa, Hanna; Väyrynen, Juha P.; Wirta, Erkki-Ville; Kuopio, Teijo; Helminen, Olli; Seppälä, Toni T.; Kellokumpu, Ilmo; Mecklin, Jukka-Pekka (MDPI AG, 2021)Purpose: To evaluate immune cell infiltration, the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) expression and their prognostic value in a series of mismatch proficient (pMMR) CRC with matched liver and lung ...
Immunophenotype based on inflammatory cells, PD-1/PD-L1 signalling pathway and M2 macrophages predicts survival in gastric cancer Junttila, Anna; Helminen, Olli; Väyrynen, Juha P.; Ahtiainen, Maarit; Kenessey, Istvan; Jalkanen, Sirpa; Mecklin, Jukka-Pekka; Kellokumpu, Ilmo; Kuopio, Teijo; Böhm, Jan; Mrena, Johanna (Nature Publishing Group, 2020)Background: Immune response against cancer has prognostic impact but its role in gastric cancer is poorly known. The aim of the study was to assess the prognostic significance of immune cell score (CD3+, CD8+), tumour ...
Stromal hyaluronan accumulation is associated with low immune response and poor prognosis in pancreatic cancer Tahkola, Kyösti; Ahtiainen, Maarit; Mecklin, Jukka-Pekka; Kellokumpu, Ilmo; Laukkarinen, Johanna; Tammi, Markku; Tammi, Raija; Väyrynen, Juha P.; Böhm, Jan (Nature Publishing Group, 2021)Hyaluronan (HA) accumulation has been associated with poor survival in various cancers, but the mechanisms for this phenomenon are still unclear. The aim of this study was to investigate the prognostic significance of ...