{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T01:31:08Z","timestamp":1786325468595,"version":"build-2736575974"},"reference-count":58,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Mismatch repair deficiency (MMRd) is a central molecular determinant of colorectal cancer (CRC) biology, prognosis, and treatment response, and Universal Tumour Screening (UTS) is advocated for Lynch syndrome (LS) detection; yet real-world performance across clinical subgroups remains limited. We evaluated MMRd distribution and UTS-based LS detection in a large consecutive surgical cohort. Methods: We retrospectively analyzed 1022 consecutive CRC patients undergoing surgical resection at the University Hospital of Padua (2015\u20132023). MMR status was assessed by immunohistochemistry; MMRd cases underwent reflex BRAF mutation testing and, when available, MLH1 promoter methylation analysis, followed by germline multigene panel testing for suspected LS. Clinicopathological features were compared by MMR status, age at onset, and tumour location. Results: MMR testing was performed in 875 patients (85.6%), rising from 67.0% (2015\u20132017) to 97.4% (2021\u20132023). MMRd was identified in 139 tumors (15.9%) and was independently associated with age \u2265 70 years, colonic location, and stage 0\u2013II. Of 22 patients with confirmed LS, 13 (59.1%) were newly identified through UTS; family history showed no significant univariate association with LS status and was not independently associated with MMRd after multivariable adjustment. MMRd prevalence was numerically higher in early- than late-onset CRC (20.0% vs. 15.4%), approaching significance after multivariable adjustment (OR 1.90, 95% CI 0.99\u20133.64; p = 0.054); hereditary syndromes were also more frequent in early-onset disease. MMRd was markedly rarer in rectal than colonic cancer (4.1% vs. 22.5%; p &lt; 0.0001), though MMRd rectal cancers arose in younger patients. Conclusions: UTS identified a substantial proportion of LS carriers missed by age- or family-history criteria. The relationship between age and MMRd prevalence proved more nuanced than a simple comparison would suggest, reinforcing the value of universal over selective testing across the age spectrum, while MMRd rectal cancer shows a distinct younger profile relevant to immunotherapy-based organ preservation.<\/jats:p>","DOI":"10.3390\/cancers18162549","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T01:20:03Z","timestamp":1786324803000},"page":"2549","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Universal Tumor Screening in Colorectal Cancer: Role of MMR Immunohistochemistry for Lynch Syndrome and Early-Onset CRC"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8612-7007","authenticated-orcid":false,"given":"Silvia","family":"Negro","sequence":"first","affiliation":[{"name":"Third Surgery Unit, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Via Giustiniani 2, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lessio","sequence":"additional","affiliation":[{"name":"Third Surgery Unit, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Via Giustiniani 2, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3772-9426","authenticated-orcid":false,"given":"Daniele","family":"Passeri","sequence":"additional","affiliation":[{"name":"Third Surgery Unit, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Via Giustiniani 2, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Baldo","sequence":"additional","affiliation":[{"name":"Third Surgery Unit, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Via Giustiniani 2, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Scarpa","sequence":"additional","affiliation":[{"name":"Third Surgery Unit, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Via Giustiniani 2, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo Paolo Dei","family":"Tos","sequence":"additional","affiliation":[{"name":"Surgical Pathology and Cytopathology Unit, Department of Integrated Diagnostics, Azienda Ospedale-Universit\u00e0 Padova, 35124 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganmaria","family":"Pennelli","sequence":"additional","affiliation":[{"name":"Surgical Pathology and Cytopathology Unit, Department of Integrated Diagnostics, Azienda Ospedale-Universit\u00e0 Padova, 35124 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Schiavi","sequence":"additional","affiliation":[{"name":"Familial Cancer Clinic and Oncoendocrinology, Veneto Institute of Oncology-Scientific Institute for Research, Hospitalization and Health Care, IOV-IRCCS, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1024-1994","authenticated-orcid":false,"given":"Claudia","family":"Pinato","sequence":"additional","affiliation":[{"name":"Familial Cancer Clinic and Oncoendocrinology, Veneto Institute of Oncology-Scientific Institute for Research, Hospitalization and Health Care, IOV-IRCCS, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6515-5482","authenticated-orcid":false,"given":"Matteo","family":"Fassan","sequence":"additional","affiliation":[{"name":"Surgical Pathology and Cytopathology Unit, Department of Integrated Diagnostics, Azienda Ospedale-Universit\u00e0 Padova, 35124 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3463-6659","authenticated-orcid":false,"given":"Quoc Riccardo","family":"Bao","sequence":"additional","affiliation":[{"name":"Third Surgery Unit, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Via Giustiniani 2, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Bergamo","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit 1, Veneto Institute of Oncology-Scientific Institute for Research, Hospitalization and Health Care, IOV-IRCCS, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7593-8138","authenticated-orcid":false,"given":"Sara","family":"Lonardi","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit 1, Veneto Institute of Oncology-Scientific Institute for Research, Hospitalization and Health Care, IOV-IRCCS, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7275-2573","authenticated-orcid":false,"given":"Gaya","family":"Spolverato","sequence":"additional","affiliation":[{"name":"Third Surgery Unit, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Via Giustiniani 2, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2789-2470","authenticated-orcid":false,"given":"Emanuele Damiano Luca","family":"Urso","sequence":"additional","affiliation":[{"name":"Third Surgery Unit, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Via Giustiniani 2, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nrclinonc.2009.237","article-title":"Microsatellite instability in colorectal cancer\u2014The stable evidence","volume":"7","author":"Vilar","year":"2010","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"248","DOI":"10.32074\/1591-951X-158","article-title":"Current prognostic and predictive biomarkers for gastrointestinal tumors in clinical practice","volume":"112","author":"Fassan","year":"2020","journal-title":"Pathologica"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1111\/his.14233","article-title":"Identifying mismatch repair-deficient colon cancer: Near-perfect concordance between immunohistochemistry and microsatellite instability testing in a large, population-based series","volume":"78","author":"Loughrey","year":"2021","journal-title":"Histopathology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1136\/jclinpath-2022-208143","article-title":"MMR profile and microsatellite instability status in colorectal mucinous adenocarcinoma with synchronous metastasis: A new clue for the clinical practice","volume":"76","author":"Parente","year":"2023","journal-title":"J. Clin. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Malapelle, U., Parente, P., Pepe, F., De Luca, C., Cerino, P., Covelli, C., Balestrieri, M., Russo, G., Bonfitto, A., and Pisapia, P. (2020). Impact of Pre-Analytical Factors on MSI Test Accuracy in Mucinous Colorectal Adenocarcinoma: A Multi-Assay Concordance Study. Cells, 9.","DOI":"10.3390\/cells9092019"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1200\/JCO.2009.27.1825","article-title":"Defective Mismatch Repair As a Predictive Marker for Lack of Efficacy of Fluorouracil-Based Adjuvant Therapy in Colon Cancer","volume":"28","author":"Sargent","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1200\/JCO.2005.01.086","article-title":"Systematic Review of Microsatellite Instability and Colorectal Cancer Prognosis","volume":"23","author":"Popat","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2788","DOI":"10.1016\/j.ejca.2010.05.009","article-title":"Microsatellite instability as a marker of prognosis and response to therapy: A meta-analysis of colorectal cancer survival data","volume":"46","author":"Guastadisegni","year":"2010","journal-title":"Eur. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.ejca.2022.07.020","article-title":"Deficient mismatch repair\/microsatellite unstable colorectal cancer: Diagnosis, prognosis and treatment","volume":"175","author":"Taieb","year":"2022","journal-title":"Eur. J. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1056\/NEJMoa1500596","article-title":"PD-1 Blockade in Tumors with Mismatch-Repair Deficiency","volume":"372","author":"Le","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1056\/NEJMoa2201445","article-title":"PD-1 Blockade in Mismatch Repair\u2013Deficient, Locally Advanced Rectal Cancer","volume":"386","author":"Cercek","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1056\/NEJMoa2404512","article-title":"Nonoperative Management of Mismatch Repair\u2013Deficient Tumors","volume":"392","author":"Cercek","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/s41416-019-0599-y","article-title":"Immune checkpoint inhibitors for the treatment of MSI-H\/MMR-D colorectal cancer and a perspective on resistance mechanisms","volume":"121","author":"Sahin","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1001\/jamaoncol.2023.3323","article-title":"Neoadjuvant Immune Checkpoint Inhibitor Therapy for Localized Deficient Mismatch Repair Colorectal Cancer","volume":"9","author":"Emiloju","year":"2023","journal-title":"JAMA Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1056\/NEJMoa043146","article-title":"Screening for the Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer)","volume":"352","author":"Hampel","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5783","DOI":"10.1200\/JCO.2008.17.5950","article-title":"Feasibility of Screening for Lynch Syndrome Among Patients With Colorectal Cancer","volume":"26","author":"Hampel","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S0016-5085(00)70168-5","article-title":"Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer","volume":"118","author":"Aarnio","year":"2000","journal-title":"Gastroenterology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/ng1834","article-title":"CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer","volume":"38","author":"Weisenberger","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8698","DOI":"10.1073\/pnas.95.15.8698","article-title":"Biallelic inactivation of hMLH 1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers","volume":"95","author":"Veigl","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1006\/scbi.1999.0135","article-title":"CpG island methylator phenotypes in aging and cancer","volume":"9","author":"Toyota","year":"1999","journal-title":"Semin. Cancer Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1111\/his.15133","article-title":"BRAF V600E immunohistochemistry can reliably substitute BRAF molecular testing in the Lynch syndrome screening algorithm in colorectal cancer","volume":"84","author":"Grillo","year":"2024","journal-title":"Histopathology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1001\/jama.2012.13088","article-title":"Identification of Lynch Syndrome Among Patients With Colorectal Cancer","volume":"308","author":"Moreira","year":"2012","journal-title":"JAMA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1093\/jnci\/djh034","article-title":"Revised Bethesda Guidelines for Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) and Microsatellite Instability","volume":"96","author":"Umar","year":"2004","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"17","DOI":"10.21037\/tgh-23-71","article-title":"Family history as a major prerequisite for microsatellite instability screening in colorectal cancer is a poor selection tool","volume":"9","author":"Jakob","year":"2024","journal-title":"Transl. Gastroenterol. Hepatol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (2009). Recommendations from the EGAPP Working Group: Genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives. Genet. Med., 11, 35\u201341.","DOI":"10.1097\/GIM.0b013e31818fa2ff"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1097\/CEJ.0000000000000677","article-title":"Universal testing for MSI\/MMR status in colorectal and endometrial cancers to identify Lynch syndrome cases: State of the art in Italy and consensus recommendations from the Italian Association for the Study of Familial Gastrointestinal Tumors (A.I.F.E.G.)","volume":"31","author":"Tibiletti","year":"2022","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.1002\/cncr.31534","article-title":"Universal screening of both endometrial and colon cancers increases the detection of Lynch syndrome","volume":"124","author":"Adar","year":"2018","journal-title":"Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1001\/jamasurg.2021.2380","article-title":"Characteristics of Early-Onset vs Late-Onset Colorectal Cancer","volume":"156","author":"Zaborowski","year":"2021","journal-title":"JAMA Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1136\/gutjnl-2019-319511","article-title":"Global patterns and trends in colorectal cancer incidence in young adults","volume":"68","author":"Siegel","year":"2019","journal-title":"Gut"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e137","DOI":"10.1016\/S2468-2667(18)30267-6","article-title":"Emerging cancer trends among young adults in the USA: Analysis of a population-based cancer registry","volume":"4","author":"Sung","year":"2019","journal-title":"Lancet Public Health"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1136\/gutjnl-2019-320406","article-title":"Decline in the incidence of colorectal cancer and the associated mortality in young Italian adults","volume":"69","author":"Zorzi","year":"2020","journal-title":"Gut"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1056\/NEJMc2210175","article-title":"Prevalence of Mismatch-Repair Deficiency in Rectal Adenocarcinomas","volume":"387","author":"Papke","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1111\/his.14710","article-title":"Microsatellite instability in rectal cancer: What does it mean? A study of two randomized trials and a systematic review of the literature","volume":"81","author":"Swets","year":"2022","journal-title":"Histopathology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1097\/PAS.0000000000001918","article-title":"DNA Mismatch Repair\u2013deficient Rectal Cancer Is Frequently Associated With Lynch Syndrome and With Poor Response to Neoadjuvant Therapy","volume":"46","author":"Farchoukh","year":"2022","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1055\/s-0043-1770730","article-title":"Management of Rectal Cancer in Lynch Syndrome: Balancing Risk Reduction and Quality of Life","volume":"37","author":"Krasnick","year":"2024","journal-title":"Clin. Colon Rectal Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1055\/s-0043-1770717","article-title":"Treatment of Microsatellite-Unstable Rectal Cancer in Sporadic and Hereditary Settings","volume":"37","author":"Anderson","year":"2024","journal-title":"Clin. Colon Rectal Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/humu.22981","article-title":"HGVS Recommendations for the Description of Sequence Variants: 2016 Update","volume":"37","author":"Dalgleish","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"19","DOI":"10.7326\/M18-3316","article-title":"Comparison of Universal Versus Age-Restricted Screening of Colorectal Tumors for Lynch Syndrome Using Mismatch Repair Immunohistochemistry","volume":"171","author":"Li","year":"2019","journal-title":"Ann. Intern. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2020\/1807929","article-title":"Epidemiology of Microsatellite Instability High (MSI-H) and Deficient Mismatch Repair (dMMR) in Solid Tumors: A Structured Literature Review","volume":"2020","author":"Lorenzi","year":"2020","journal-title":"J. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"20495","DOI":"10.1038\/s41598-022-23319-1","article-title":"A scoping review and meta-analysis on the prevalence of pan-tumour biomarkers (dMMR, MSI, high TMB) in different solid tumours","volume":"12","author":"Kang","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/j.dld.2020.06.002","article-title":"Is tumor testing efficiency for Lynch syndrome different in rectal and colon cancer?","volume":"52","author":"Marabelli","year":"2020","journal-title":"Dig. Liver Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13053-023-00266-0","article-title":"Diagnosis of patients with Lynch syndrome lacking the Amsterdam II or Bethesda criteria","volume":"21","year":"2023","journal-title":"Hered. Cancer Clin. Pract."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41436-019-0596-9","article-title":"Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: Findings from the Prospective Lynch Syndrome Database","volume":"22","author":"Sampson","year":"2020","journal-title":"Genet. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1016\/j.ejca.2013.01.029","article-title":"Are the common genetic variants associated with colorectal cancer risk for DNA mismatch repair gene mutation carriers?","volume":"49","author":"Win","year":"2013","journal-title":"Eur. J. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"695","DOI":"10.6004\/jnccn.2024.0061","article-title":"Genetic\/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric, Version 3.2024, NCCN Clinical Practice Guidelines In Oncology","volume":"22","author":"Hodan","year":"2024","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.dld.2018.02.009","article-title":"Early onset sporadic colorectal cancer: Worrisome trends and oncogenic features","volume":"50","author":"Cavestro","year":"2018","journal-title":"Dig. Liver Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1001\/jamaoncol.2016.5194","article-title":"Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer","volume":"3","author":"Pearlman","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.cgh.2022.12.006","article-title":"Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines","volume":"21","author":"Cavestro","year":"2023","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Daca Alvarez, M., Quintana, I., Terradas, M., Mur, P., Balaguer, F., and Valle, L. (2021). The Inherited and Familial Component of Early-Onset Colorectal Cancer. Cells, 10.","DOI":"10.3390\/cells10030710"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1007\/s10147-015-0935-z","article-title":"Colorectal cancer in young patients: Is it a distinct clinical entity?","volume":"21","author":"Goldvaser","year":"2016","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1038\/modpathol.2012.61","article-title":"Clinicopathologic and molecular features of sporadic early-onset colorectal adenocarcinoma: An adenocarcinoma with frequent signet ring cell differentiation, rectal and sigmoid involvement, and adverse morphologic features","volume":"25","author":"Chang","year":"2012","journal-title":"Mod. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Spolverato, G., Capelli, G., Battagello, J., Barina, A., Nordio, S., Finotti, E., Mondi, I., Da Lio, C., Morpurgo, E., and Navarro, J.A. (2021). More Favorable Short and Long-Term Outcomes for Screen-Detected Colorectal Cancer Patients. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.620644"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s13244-015-0414-0","article-title":"Imaging body composition in cancer patients: Visceral obesity, sarcopenia and sarcopenic obesity may impact on clinical outcome","volume":"6","author":"Yip","year":"2015","journal-title":"Insights Imaging"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1136\/gutjnl-2013-304701","article-title":"Obesity and colorectal cancer","volume":"62","author":"Bardou","year":"2013","journal-title":"Gut"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3511","DOI":"10.1200\/JCO.2022.40.16_suppl.3511","article-title":"Neoadjuvant nivolumab, ipilimumab, and celecoxib in MMR-proficient and MMR-deficient colon cancers: Final clinical analysis of the NICHE study","volume":"40","author":"Verschoor","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1056\/NEJMoa2017699","article-title":"Pembrolizumab in Microsatellite-Instability\u2013High Advanced Colorectal Cancer","volume":"383","author":"Shiu","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Pastorino, R., Basile, M., Tognetto, A., Di Marco, M., Grossi, A., Lucci-Cordisco, E., Scaldaferri, F., De Censi, A., Federici, A., and Villari, P. (2020). Cost-effectiveness analysis of genetic diagnostic strategies for Lynch syndrome in Italy. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0235038"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Hao, J., Hassen, D., Gudgeon, J.M., Snyder, S.R., Hampel, H., Williams, M.S., Sharaf, R.N., Lu, C.Y., Williams, J.L., and Schlieder, V. (2021). Economic Evaluation of Universal Lynch Syndrome Screening Protocols among Newly Diagnosed Patients with Colorectal Cancer. J. Pers. Med., 11.","DOI":"10.3390\/jpm11121284"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/16\/2549\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T01:25:21Z","timestamp":1786325121000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/16\/2549"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,8]]},"references-count":58,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cancers18162549"],"URL":"https:\/\/doi.org\/10.3390\/cancers18162549","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,8]]}}}