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Onkologische Welt 2020; 11(05): 232-238
DOI: 10.1055/a-1268-3713
Originalartikel

Labordiagnostik bei gastrointestinalen Tumoren

Molekulare Biomarker und deren Rolle im Krebsscreening, der Detektion von Rezidiven sowie als prognostische und prädiktive Faktoren
Marcus Kleber∗
1   V. Medizinische Klinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim
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ZUSAMMENFASSUNG

Das kolorektale Karzinom (KRK) ist einer der häufigsten malignen Tumoren in Deutschland. Einer frühzeitigen Diagnostik kommt große Bedeutung zu. Goldstandard ist hier die Koloskopie. Die aktuelle S3-Leitlinie Kolorektales Karzinom empfiehlt zum KRK-Screening den fäkalen okkulten Bluttest. Für das Monitoring von Patienten vor und nach Tumorresektion werden die Messung des Carcinoembryonalen Antigens (CEA) und der Mikrosatellitenstabilität empfohlen. Für die Auswahl der korrekten Chemotherapie scheint derzeit eine Überprüfung des Mutationsstatus, mindestens des KRAS-Gens und des BRAF-Gens, sinnvoll zu sein. Eine Reihe an neuartigen Tumormarkern befindet sich momentan in der Entwicklung, hat jedoch noch nicht die Reife für eine mögliche Anwendung in der Routinediagnostik erreicht. Den schnellsten Weg in die breite Anwendung können Next-Generation-Sequencing-basierte genetische Tests finden.



Publication History

Article published online:
04 November 2020

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  • Literatur

  • 1 [Anonym]. Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): S3-Leitlinie Kolorektales Karzinom, Langversion 2.1 2019 AWMF Registrierungsnummer: 021/007OL. In; 2019.
    Google Scholar
  • 2 Winawer S, Fletcher R, Rex D. et al Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence. Gastroenterology 2003; 124: 544-560
    CrossrefPubMedGoogle Scholar
  • 3 Doran J, Hardcastle JD. Bleeding patterns in colorectal cancer: the effect of aspirin and the implications for faecal occult blood testing. The British journal of surgery 1982; 69: 711-713
    CrossrefPubMedGoogle Scholar
  • 4 Macrae FA, St John DJ. Relationship between patterns of bleeding and Hemoccult sensitivity in patients with colorectal cancers or adenomas. Gastroenterology 1982; 82: 891-898
    CrossrefPubMedGoogle Scholar
  • 5 Hewitson P, Glasziou P, Irwig L. et al Screening for colorectal cancer using the faecal occult blood test, Hemoccult. Cochrane Database Syst Rev 2007
    PubMedGoogle Scholar
  • 6 Hundt S, Haug U, Brenner H. Comparative evaluation of immunochemical fecal occult blood tests for colorectal adenoma detection. Annals of internal medicine 2009; 150: 162-169
    CrossrefPubMedGoogle Scholar
  • 7 Goldstein MJ, Mitchell EP. Carcinoembryonic antigen in the staging and follow-up of patients with colorectal cancer. Cancer Invest 2005; 23: 338-351
    CrossrefPubMedGoogle Scholar
  • 8 Mala T, Bohler G, Mathisen O. et al Hepatic resection for colorectal metastases: can preoperative scoring predict patient outcome?. World J Surg 2002; 26: 1348-1353
    CrossrefPubMedGoogle Scholar
  • 9 Israelsen WJ, Vander Heiden MG. Pyruvate kinase: Function, regulation and role in cancer. Semin Cell Dev Biol 2015; 43: 43-51
    CrossrefPubMedGoogle Scholar
  • 10 Haug U, Hundt S, Brenner H. Sensitivity and specificity of faecal tumour M2 pyruvate kinase for detection of colorectal adenomas in a large screening study. British journal of cancer 2008; 99: 133-135
    CrossrefPubMedGoogle Scholar
  • 11 Pellegrini P, Contasta I, Berghella AM. et al Simultaneous measurement of soluble carcinoembryonic antigen and the tissue inhibitor of metalloproteinase TIMP1 serum levels for use as markers of pre-invasive to invasive colorectal cancer. Cancer Immunol Immunother 2000; 49: 388-394
    CrossrefPubMedGoogle Scholar
  • 12 Nicolini A, Ferrari P, Duffy MJ. et al Intensive risk-adjusted follow-up with the CEA, TPA, CA19.9, and CA72.4 tumor marker panel and abdominal ultrasonography to diagnose operable colorectal cancer recurrences: effect on survival. Arch Surg 2010; 145: 1177-1183
    CrossrefPubMedGoogle Scholar
  • 13 Lumachi F, Marino F, Orlando R. et al Simultaneous multianalyte immunoassay measurement of five serum tumor markers in the detection of colorectal cancer. Anticancer Res 2012; 32: 985-988
    Google Scholar
  • 14 Zhou W, Yang F, Peng J. et al High pretreatment serum CA19-9 level predicts a poor prognosis for patients with stage III colon cancer after curative resection and adjuvant chemotherapy. J Cancer 2019; 10: 3810-3818
    CrossrefPubMedGoogle Scholar
  • 15 Popat S, Hubner R, Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol 2005; 23: 609-618
    CrossrefPubMedGoogle Scholar
  • 16 Gkekas I, Novotny J, Pecen L. et al Microsatellite Instability as a Prognostic Factor in Stage II Colon Cancer Patients, a Meta-Analysis of Published Literature. Anticancer Res 2017; 37: 6563-6574
    Google Scholar
  • 17 Martinez-Lopez E, Abad A, Font A. et al Allelic loss on chromosome 18q as a prognostic marker in stage II colorectal cancer. Gastroenterology 1998; 114: 1180-1187
    CrossrefPubMedGoogle Scholar
  • 18 Diep CB, Thorstensen L, Meling GI. et al Genetic tumor markers with prognostic impact in Dukes’ stages B and C colorectal cancer patients. J Clin Oncol 2003; 21: 820-829
    CrossrefPubMedGoogle Scholar
  • 19 Araujo SE, Bernardo WM, Habr-Gama A. et al DNA ploidy status and prognosis in colorectal cancer: a meta-analysis of published data. Dis Colon Rectum 2007; 50: 1800-1810
    CrossrefPubMedGoogle Scholar
  • 20 Ogino S, Nosho K, Irahara N. et al Prognostic significance and molecular associations of 18q loss of heterozygosity: a cohort study of microsatellite stable colorectal cancers. J Clin Oncol 2009; 27: 4591-4598
    CrossrefPubMedGoogle Scholar
  • 21 Dong SM, Traverso G, Johnson C. et al Detecting colorectal cancer in stool with the use of multiple genetic targets. J Natl Cancer Inst 2001; 93: 858-865
    CrossrefPubMedGoogle Scholar
  • 22 Imperiale TF, Ransohoff DF, Itzkowitz SH. et al Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. The New England journal of medicine 2004; 351: 2704-2714
    CrossrefPubMedGoogle Scholar
  • 23 Douillard JY, Oliner KS, Siena S. et al Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. The New England journal of medicine 2013; 369: 1023-1034
    CrossrefPubMedGoogle Scholar
  • 24 Sorich MJ, Wiese MD, Rowland A. et al Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer: a meta-analysis of randomized, controlled trials. Annals of oncology : official journal of the European Society for Medical Oncology 2015; 26: 13-21
    CrossrefPubMedGoogle Scholar
  • 25 Karapetis CS, Khambata-Ford S, Jonker DJ. et al K-ras mutations and benefit from cetuximab in advanced colorectal cancer. The New England journal of medicine 2008; 359: 1757-1765
    CrossrefPubMedGoogle Scholar
  • 26 Tran B, Kopetz S, Tie J. et al Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer 2011; 117: 4623-4632
    CrossrefPubMedGoogle Scholar
  • 27 Tejpar S, Bertagnolli M, Bosman F. et al Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery. Oncologist 2010; 15: 390-404
    CrossrefPubMedGoogle Scholar
  • 28 Liao X, Morikawa T, Lochhead P. et al Prognostic role of PIK3CA mutation in colorectal cancer: cohort study and literature review. Clin Cancer Res 2012; 18: 2257-2268
    CrossrefPubMedGoogle Scholar
  • 29 Peach G, Kim C, Zacharakis E. et al Prognostic significance of circulating tumour cells following surgical resection of colorectal cancers: a systematic review. British journal of cancer 2010; 102: 1327-1334
    CrossrefPubMedGoogle Scholar
  • 30 Reimers N, Pantel K. Liquid biopsy: novel technologies and clinical applications. Clinical chemistry and laboratory medicine : CCLM/FESCC 2019; 57: 312-316
    CrossrefPubMedGoogle Scholar
  • 31 Reinert T, Scholer LV, Thomsen R. et al Analysis of circulating tumour DNA to monitor disease burden following colorectal cancer surgery. Gut 2016; 65: 625-634
    CrossrefPubMedGoogle Scholar
  • 32 Cai L, Hood S, Kallam E. et al Epi proColon® Use of a Non-Invasive SEPT9 Gene Methylation Blood Test for Colorectal Cancer Screening: A National Laboratory Experience. J Clin Epigenet 2018 DOI: doi:10.21767/2472–1158.100092: 4:7. doi:10.21767/2472–1158.100092
    CrossrefGoogle Scholar
  • 33 Church TR, Wandell M, Lofton-Day C. et al Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer. Gut 2014; 63: 317-325
    CrossrefPubMedGoogle Scholar
  • 34 Sun H, Wang P, Zhang Q. et al MicroRNA21 expression is associated with the clinical features of patients with gastric carcinoma and affects the proliferation, invasion and migration of gastric cancer cells by regulating Noxa. Mol Med Rep 2016; 13: 2701-2707
    CrossrefPubMedGoogle Scholar
  • 35 Yan F, Wang C, Li T. et al Role of miR-21 in the growth and metastasis of human salivary adenoid cystic carcinoma. Mol Med Rep 2018; 17: 4237-4244
    PubMedGoogle Scholar
  • 36 Chen H, Liu H, Zou H. et al Evaluation of Plasma miR-21 and miR-152 as Diagnostic Biomarkers for Common Types of Human Cancers. J Cancer 2016; 7: 490-499
    CrossrefPubMedGoogle Scholar
  • 37 Kanaan Z, Rai SN, Eichenberger MR. et al Plasma miR-21: a potential diagnostic marker of colorectal cancer. Annals of surgery 2012; 256: 544-551
    CrossrefPubMedGoogle Scholar