{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T06:17:38Z","timestamp":1788675458837,"version":"build-2803163510"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Gastrointest Canc"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Purpose<\/jats:title>\n            <jats:p>Lynch syndrome is an autosomal dominant genetic disorder associated with early-onset colorectal cancer (CRC), endometrial cancer and other malignancies. This condition is defined by deficient DNA mismatch repair and high microsatellite instability (dMMR\/MSI-high), exhibiting a substantial response to immunotherapy. However, microsatellite-stable (MSS) tumours may infrequently occur in individuals with Lynch syndrome. Our aim was to evaluate the efficacy of immunotherapy in patients with Lynch Syndrome and dMMR\/MSS colorectal cancer.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>A systematic review of the literature in medical databases, major related conferences and relevant oncology journals was conducted to identify the available evidence. Medical records from the Medical and Clinical Oncology Department of the University Hospital of Ioannina were also reviewed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Four cases of MSS colorectal cancer associated with Lynch syndrome and MSH6 germline mutation were identified. Three of these four patients were treated with immune checkpoint inhibitors. Two patients with metastatic disease experienced disease progression, but one patient who received neoadjuvant immunotherapy achieved a partial response. All four patients were diagnosed with colorectal cancer in ages younger than 52 (16\u201351\u00a0years old).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>MSS CRC tumours in patients with Lynch syndrome is an infrequent phenomenon and under-represented in the literature. The limited efficacy of immune checkpoint inhibitors is highlighted in this rare subset of patients.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s12029-025-01203-1","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T21:06:51Z","timestamp":1743196011000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Microsatellite Stable Colorectal Tumours in Patients with Lynch Syndrome: A Case Report and Systematic Review Analysing Clinical Features and Implications for Immunotherapy"],"prefix":"10.1007","volume":"56","author":[{"given":"Fani","family":"Kapoulitsa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Mauri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos K.","family":"Tsilidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Katsanos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Timotheadou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Smaragdi","family":"Vlachou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Kamposioras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"issue":"1","key":"1203_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1399-0004.2009.01230.x","volume":"76","author":"HT Lynch","year":"2009","unstructured":"Lynch HT, Lynch PM, Lanspa SJ, et al. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet. 2009;76(1):1\u201318. https:\/\/doi.org\/10.1111\/j.1399-0004.2009.01230.x.","journal-title":"Clin Genet"},{"issue":"1","key":"1203_CR2","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/s41436-020-0892-4","volume":"22","author":"M Dominguez-Valentin","year":"2020","unstructured":"Dominguez-Valentin M, Sampson JR, Sepp\u00e4l\u00e4 TT, et al. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database. Genet Med. 2020;22(1):15\u201325. https:\/\/doi.org\/10.1038\/s41436-020-0892-4.","journal-title":"Genet Med"},{"issue":"3","key":"1203_CR3","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1200\/JCO.2024.42.3_suppl.175","volume":"42","author":"C Eslinger","year":"2024","unstructured":"Eslinger C, McGary A, Walden D, et al. Outcomes with immunotherapy between Lynch syndrome vs non-Lynch syndrome microsatellite instability-high colorectal cancer. J Clin Oncol. 2024;42(3):175. https:\/\/doi.org\/10.1200\/JCO.2024.42.3_suppl.175.","journal-title":"J Clin Oncol"},{"key":"1203_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2023.113253","volume":"192","author":"JH Yu","year":"2023","unstructured":"Yu JH, Xiao BY, Tang JH, et al. Efficacy of PD-1 inhibitors for colorectal cancer and polyps in Lynch syndrome patients. Eur J Cancer. 2023Oct;192: 113253. https:\/\/doi.org\/10.1016\/j.ejca.2023.113253.","journal-title":"Eur J Cancer"},{"issue":"13","key":"1203_CR5","doi-asserted-by":"publisher","first-page":"8009","DOI":"10.2147\/CMAR.S333690","volume":"21","author":"Q Gou","year":"2021","unstructured":"Gou Q, Xie Y, Zhang M, et al. Synchronous rectal tumours with different molecular and genetic phenotypes occurring in a patient with Lynch syndrome. Cancer Manag Res. 2021;21(13):8009\u201315. https:\/\/doi.org\/10.2147\/CMAR.S333690.","journal-title":"Cancer Manag Res"},{"issue":"9","key":"1203_CR6","doi-asserted-by":"publisher","first-page":"550","DOI":"10.3389\/fonc.2019.00550","volume":"26","author":"S Sun","year":"2019","unstructured":"Sun S, Liu Y, Eisfeld AK, Zhen F, et al. Identification of germline mismatch repair gene mutations in lung cancer patients with paired tumor-normal next generation sequencing: a retrospective study. Front Oncol. 2019;26(9):550. https:\/\/doi.org\/10.3389\/fonc.2019.00550.","journal-title":"Front Oncol"},{"issue":"3","key":"1203_CR7","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1016\/j.ygyno.2021.11.008","volume":"162","author":"M Rasmussen","year":"2021","unstructured":"Rasmussen M, Lim K, Rambech E, et al. Lynch syndrome-associated epithelial ovarian cancer and its immunological profile. Gynecol Oncol. 2021;162(3):686\u201393. https:\/\/doi.org\/10.1016\/j.ygyno.2021.11.008.","journal-title":"Gynecol Oncol"},{"issue":"3","key":"1203_CR8","doi-asserted-by":"publisher","first-page":"467","DOI":"10.3390\/cancers13030467","volume":"13","author":"J Leclerc","year":"2021","unstructured":"Leclerc J, Vermaut C, Buisine MP. Diagnosis of Lynch syndrome and strategies to distinguish Lynch-related tumors from sporadic MSI\/dMMR tumors. Cancers (Basel). 2021;13(3):467. https:\/\/doi.org\/10.3390\/cancers13030467.","journal-title":"Cancers (Basel)"},{"issue":"3","key":"1203_CR9","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1007\/s10689-016-9884-6","volume":"15","author":"Z Gatalica","year":"2016","unstructured":"Gatalica Z, Vranic S, Xiu J, et al. High microsatellite instability (MSI-H) colorectal carcinoma: a brief review of predictive biomarkers in the era of personalized medicine. Fam Cancer. 2016;15(3):405\u201312. https:\/\/doi.org\/10.1007\/s10689-016-9884-6.","journal-title":"Fam Cancer"},{"issue":"6","key":"1203_CR10","doi-asserted-by":"publisher","first-page":"2073","DOI":"10.1053\/j.gastro.2009.12.064","volume":"138","author":"CR Boland","year":"2010","unstructured":"Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology. 2010;138(6):2073\u201387. https:\/\/doi.org\/10.1053\/j.gastro.2009.12.064.","journal-title":"Gastroenterology"},{"issue":"3","key":"1203_CR11","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1111\/his.14233","volume":"78","author":"MB Loughrey","year":"2021","unstructured":"Loughrey MB, McGrath J, Coleman HG, et al. Identifying mismatch repair-deficient colon cancer: near-perfect concordance between immunohistochemistry and microsatellite instability testing in a large, population-based series. Histopathology. 2021;78(3):401\u201313. https:\/\/doi.org\/10.1111\/his.14233.","journal-title":"Histopathology."},{"issue":"12","key":"1203_CR12","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2021-053538","volume":"11","author":"JA Durhuus","year":"2021","unstructured":"Durhuus JA, Therkildsen C, Kallemose T, et al. Colorectal cancer in adolescents and young adults with Lynch syndrome: a Danish register-based study. BMJ Open. 2021;11(12): e053538. https:\/\/doi.org\/10.1136\/bmjopen-2021-053538.","journal-title":"BMJ Open"},{"issue":"1","key":"1203_CR13","doi-asserted-by":"publisher","first-page":"260","DOI":"10.21037\/jgo-24-4","volume":"15","author":"J Zhang","year":"2024","unstructured":"Zhang J, Li S, Ma P, et al. Clinicopathological features and prognoses in younger and older patients with mismatch repair defects colorectal cancer: a retrospective comparative cohort study. J Gastrointest Oncol. 2024;15(1):260\u201370. https:\/\/doi.org\/10.21037\/jgo-24-4.","journal-title":"J Gastrointest Oncol."},{"issue":"2","key":"1203_CR14","first-page":"82","volume":"30","author":"R Schneider","year":"2014","unstructured":"Schneider R, Schneider C, Jakobeit C, F\u00fcrst A, M\u00f6slein G. Gender-specific aspects of lynch syndrome and familial adenomatous polyposis. Viszeralmedizin. 2014;30(2):82\u20138.","journal-title":"Viszeralmedizin"},{"issue":"2","key":"1203_CR15","doi-asserted-by":"publisher","first-page":"92","DOI":"10.3816\/CCC.2003.n.015","volume":"3","author":"CL Scaife","year":"2003","unstructured":"Scaife CL, Rodriguez-Bigas MA. Lynch syndrome: implications for the surgeon. Clin Colorectal Cancer. 2003;3(2):92\u20138. https:\/\/doi.org\/10.3816\/CCC.2003.n.015.","journal-title":"Clin Colorectal Cancer"},{"issue":"5","key":"1203_CR16","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/S1470-2045(22)00197-8","volume":"23","author":"LA Diaz Jr","year":"2022","unstructured":"Diaz LA Jr, Shiu KK, Kim TW, et al. KEYNOTE-177 Investigators. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022;23(5):659\u201370. https:\/\/doi.org\/10.1016\/S1470-2045(22)00197-8.","journal-title":"Lancet Oncol"},{"issue":"21","key":"1203_CR17","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1056\/NEJMoa2400634","volume":"390","author":"M Chalabi","year":"2024","unstructured":"Chalabi M, Verschoor YL, Tan PB, et al. Neoadjuvant immunotherapy in locally advanced mismatch repair-deficient colon cancer. N Engl J Med. 2024;390(21):1949\u201358. https:\/\/doi.org\/10.1056\/NEJMoa2400634.","journal-title":"N Engl J Med"},{"issue":"1","key":"1203_CR18","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1007\/s00384-023-04553-z","volume":"38","author":"W Yang","year":"2023","unstructured":"Yang W, Zheng H, Lv W, et al. Current status and prospect of immunotherapy for colorectal cancer. Int J Colorectal Dis. 2023;38(1):266. https:\/\/doi.org\/10.1007\/s00384-023-04553-z.","journal-title":"Int J Colorectal Dis"},{"key":"1203_CR19","doi-asserted-by":"publisher","DOI":"10.1200\/PO.22.00675","volume":"7","author":"M Ranganathan","year":"2023","unstructured":"Ranganathan M, Sacca RE, Trottier M, Maio A, Kemel Y, Salo-Mullen E, Catchings A, Kane S, Wang C, Ravichandran V, Ptashkin R, Mehta N, Garcia-Aguilar J, Weiser MR, Donoghue MTA, Berger MF, Mandelker D, Walsh MF, Carlo M, Liu YL, Cercek A, Yaeger R, Saltz L, Segal NH, Mendelsohn RB, Markowitz AJ, Offit K, Shia J, Stadler ZK, Latham A. Prevalence and clinical implications of mismatch repair-proficient colorectal cancer in patients with Lynch syndrome. JCO Precis Oncol. 2023;7: e2200675. https:\/\/doi.org\/10.1200\/PO.22.00675.","journal-title":"JCO Precis Oncol"}],"container-title":["Journal of Gastrointestinal Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12029-025-01203-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12029-025-01203-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12029-025-01203-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T21:06:58Z","timestamp":1743196018000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12029-025-01203-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,25]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["1203"],"URL":"https:\/\/doi.org\/10.1007\/s12029-025-01203-1","relation":{},"ISSN":["1941-6628","1941-6636"],"issn-type":[{"value":"1941-6628","type":"print"},{"value":"1941-6636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,25]]},"assertion":[{"value":"9 March 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2025","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that this research is performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its subsequent amendments. Institutional Review Board (IRB) approval was granted. The subject involved gave their informed consent prior to the inclusion in this case series and provided informed consent for publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval and Consent to Participate and Publish"}},{"value":"This manuscript has not been published elsewhere in any language, nor is it under consideration for publication by another journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosure"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"86"}}