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 ...
The “unnatural” history of colorectal cancer in Lynch syndrome : lessons from colonoscopy surveillance Ahadova, Aysel; Seppälä, Toni T.; Engel, Christoph; Gallon, Richard; Burn, John; Holinski‐Feder, Elke; Steinke‐Lange, Verena; Möslein, Gabriela; Nielsen, Maartje; ten Broeke, Sanne; Laghi, Luigi; Dominguez‐Valentin, Mev; Capella, Gabriel; Macrae, Finlay; Scott, Rodney; Hüneburg, Robert; Nattermann, Jacob; Hoffmeister, Michael; Brenner, Hermann; Bläker, Hendrik; von Knebel Doeberit,z Magnus; Sampson, Julian R.; Vasen, Hans; Mecklin, Jukka‐Pekka; Møller, Pål; Kloor, Matthias (Wiley, 2021)Individuals with Lynch syndrome (LS), one of the most common inherited cancer syndromes, are at increased risk of developing malignancies, in particular colorectal cancer (CRC). Regular colonoscopy with polypectomy is ...
Lack of association between screening interval and cancer stage in Lynch syndrome may be accounted for by over-diagnosis; a prospective Lynch syndrome database report Seppälä, Toni T.; Ahadova, Aysel; Dominguez-Valentin, Mev; Macrae, Finlay; Evans, D. Gareth; Therkildsen, Christina; Sampson, Julian; Scott, Rodney; Burn, John; Möslein, Gabriela; Bernstein, Inge; Holinski-Feder, Elke; Pylvänäinen, Kirsi; Renkonen-Sinisalo, Laura; Lepistö, Anna; Lautrup, Charlotte Kvist; Lindblom, Annika; Plazzer, John-Paul; Winship, Ingrid; Tjandra, Douglas; Katz, Lior H.; Aretz, Stefan; Hüneburg, Robert; Holzapfel, Stefanie; Heinimann, Karl; Valle, Adriana Della; Neffa, Florencia; Gluck, Nathan; Cappel, Wouter H. de Vos tot Nederveen; Vasen, Hans; Morak, Monika; Steinke-Lange, Verena; Engel, Christoph; Rahner, Nils; Schmiegel, Wolff; Vangala, Deepak; Thomas, Huw; Green, Kate; Lalloo, Fiona; Crosbie, Emma J.; Hill, James; Capella, Gabriel; Pineda, Marta; Navarro, Matilde; Blanco, Ignacio; Broeke, Sanne ten; Nielsen, Maartje; Ljungmann, Ken; Nakken, Sigve; Lindor, Noralane; Frayling, Ian; Hovig, Eivind; Sunde, Lone; Kloor, Matthias; Mecklin, Jukka-Pekka; Kalager, Mette; Møller, Pål (BioMed Central Ltd., 2019)Background Recent epidemiological evidence shows that colorectal cancer (CRC) continues to occur in carriers of pathogenic mismatch repair (path_MMR) variants despite frequent colonoscopy surveillance in expert centres. ...
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 ...
Converging endometrial and ovarian tumorigenesis in Lynch syndrome : shared origin of synchronous carcinomas Niskakoski, Anni; Pasanen, Annukka; Porkka, Noora; Eldfors, Samuli; Lassus, Heini; Renkonen-Sinisalo, Laura; Kaur, Sippy; Mecklin, Jukka-Pekka; Bützowb, Ralf; Peltomäki, Päivi (Academic Press, 2018)Objective The diagnosis of carcinoma in both the uterus and the ovary simultaneously is not uncommon and raises the question of synchronous primaries vs. metastatic disease. Targeted sequencing of sporadic synchronous ...