Skip to main content
SpringerLink
Log in

Nichtserratierte Vorläuferläsionen von Tumoren des Dickdarms

Non-serrated precursor lesions of colorectal tumours

  • Hauptreferate
  • Published:
Der Pathologe Aims and scope Submit manuscript

Zusammenfassung

Nichtserratierte Vorläuferläsionen von Tumoren des Dickdarms umfassen die klassischen (tubulären, tubulovillösen und villösen) Adenome und die Dysplasie (intraepitheliale Neoplasie) bei chronisch-entzündlichen Darmerkrankungen und bei den seltenen hamartomatösen Polyposesyndromen. Diese kurze Übersicht fasst die aktuelle Literatur zum Thema Adenom-Karzinom-Sequenz zusammen. Besondere Berücksichtigung erfahren dabei die Themenkomplexe Kolonstammzellen und funktionelle Organisation der Krypte sowie klonale Konversion in der Formation des monokryptalen Adenoms. Die Bedeutung einer klonalen Interaktion zwischen benachbarten Krypten sowie die Genese (großer) monoklonaler Adenome aus (kleinen) polyklonalen Vorläuferläsionen wird diskutiert. Am Ende der Übersicht wird auf die molekulare Tumorentstehung und deren klinische Bedeutung bei den chronisch-entzündlichen Darmerkrankungen und bei den hamartomatösen Polyposesyndromen eingegangen.

Abstract

Non-serrated precursor lesions of colorectal tumours include conventional adenomas (tubular, tubulovillous and villous), inflammatory bowel disease-associated dysplasia (intraepithelial neoplasia), and hamartoma-associated dysplasia. This short review summarizes the current literature on the adenoma-carcinoma sequence, focusing on colonic stem cells and functional crypt organization, patterns of stem cell division, niche succession and clonal conversion in the formation of a monocryptal adenoma. The process of clonal interaction between neighboring crypts as well as the development of large monoclonal adenomas from small polyclonal precursor lesions is discussed in detail. Finally, the molecular pathogenesis as well as the clinical significance of inflammatory bowel disease- and hamartoma-associated carcinogenesis is addressed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3
Abb. 4
Abb. 5
Abb. 6

Literatur

  1. Baretton GB, Aust DE (2008) Intraepitheliale Neoplasie / Dysplasie – Diagnose bei Colitis ulcerosa. Pathologe 29:280–285

    Article  PubMed  Google Scholar 

  2. Brabletz S, Schmalhofer O, Brabletz T (2009) Gastrointestinal stem cells in development and cancer. J Pathol 217:307–317

    Article  PubMed  CAS  Google Scholar 

  3. Calva D, Howe JR (2008) Hamartomatous polyposis syndromes. Surg Clin North Am 88:779–817

    Article  PubMed  Google Scholar 

  4. Chen HM, Fang JY (2009) Genetics of the hamartomatous polyposis syndromes: a molecular review. Int J Colorectal Dis 24:865–874

    Article  PubMed  Google Scholar 

  5. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767

    Article  PubMed  CAS  Google Scholar 

  6. Fearon ER (2011) Molecular genetics of colorectal cancer. Annu Rev Pathol 6:479–507

    Article  PubMed  CAS  Google Scholar 

  7. Esteller M, Sparks A, Toyota M et al (2000) Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer. Cancer Res 60:4366–4371

    PubMed  CAS  Google Scholar 

  8. Hiraoka S, Kato J, Tatsukawa M et al (2006) Laterally spreading type of colorectal adenoma exhibits a unique methylation phenotype and K-ras mutations. Gastroenterology 131:379–389

    Article  PubMed  CAS  Google Scholar 

  9. Humphries A, Wright NA (2008) Colonic crypt organization and tumorigenesis. Nat Rev Cancer 8:415–424

    Article  PubMed  CAS  Google Scholar 

  10. Hurlstone DP, Cross SS, Drew K et al (2004) An evaluation of colorectal endoscopic mucosal resection using high-magnification chromoscopic colonoscopy: a prospective study of 1000 colonoscopies. Endoscopy 36:491–498

    Article  PubMed  CAS  Google Scholar 

  11. Kaku E, Oda Y, Murakami Y et al (2011) Proportion of flat- and depressed-type and laterally spreading tumor among advanced colorectal neoplasia. Clin Gastroenterol Hepatol 9:503–508

    Article  PubMed  Google Scholar 

  12. Kim BC, Chang HJ, Han KS et al (2011) Clinicopathological differences of laterally spreading tumors of the colorectum according to gross appearance. Endoscopy 43:100–107

    Article  PubMed  CAS  Google Scholar 

  13. Kudo S, Lambert R, Allen JI et al (2008) Nonpolypoid neoplastic lesions of the colorectal mucosa. Gastrointest Endosc 68:S3–S47

    Article  PubMed  Google Scholar 

  14. Lash RH, Genta RM, Schuler CM (2010) Sessile serrated adenomas: prevalence of dysplasia and carcinoma in 2139 patients. J Clin Pathol 63:681–686

    Article  PubMed  Google Scholar 

  15. Merritt AJ, Gould KA, Dove WF (1997) Polyclonal structure of intestinal adenomas in ApcMin / + mice with concomitant loss of Apc + from all tumor lineages. Proc Natl Acad Sci U S A 94:13927–13931

    Article  PubMed  CAS  Google Scholar 

  16. Morin PJ, Sparks AB, Korinek V et al (1997) Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 275:1787–1790

    Article  PubMed  CAS  Google Scholar 

  17. Novelli MR, Williamson JA, Tomlinson IP et al (1996) Polyclonal origin of colonic adenomas in an XO / XY patient with FAP. Science 272:1187–1190

    Article  PubMed  CAS  Google Scholar 

  18. Odze RD, Riddell RH, Bosman FT et al (2010) Premalignant lesions of the digestive system. In: Bosman FT, Carneiro F, Hruban RH, Theise ND (eds) WHO classification of tumours of the digestive system. IARC, Lyon, pp 10–12

  19. Parra-Blanco A, Gimeno-García AZ, Nicolás-Pérez D et al (2006) Risk for high-grade dysplasia or invasive carcinoma in colorectal flat adenomas in a Spanish population. Gastroenterol Hepatol 29:602–609

    PubMed  Google Scholar 

  20. Pino MS, Chung DC (2010) The chromosomal instability pathway in colon cancer. Gastroenterology 138:2059–2072

    Article  PubMed  CAS  Google Scholar 

  21. Radtke F, Clevers H (2005) Self-renewal and cancer of the gut: two sides of a coin. Science 307:1904–1909

    Article  PubMed  CAS  Google Scholar 

  22. Reya T, Clevers H (2005) Wnt signalling in stem cells and cancer. Nature 434:843–850

    Article  PubMed  CAS  Google Scholar 

  23. Ricci-Vitiani L, Pagliuca A, Palio E et al (2008) Colon cancer stem cells. Gut 57:538–548

    Article  PubMed  CAS  Google Scholar 

  24. Ricci-Vitiani L, Fabrizi E, Palio E, De Maria R (2009) Colon cancer stem cells. J Mol Med 87:1097–1104

    Article  PubMed  Google Scholar 

  25. Rüschoff J, Heinmöller E, Hartmann A et al (2010) Differenzialdiagnostik erblicher Dickdarmkarzinomsyndrome. Der Beitrag der Pathologie. Pathologe 31:412–422

    Article  PubMed  Google Scholar 

  26. Sanchez JA, Dejulius KL, Bronner M et al (2011) Relative role of methylator and tumor suppressor pathways in ulcerative colitis-associated colon cancer. Inflamm Bowel Dis. doi:10.1002 / ibd.21526. [Epub ahead of print]

  27. Spring KJ, Zhao ZZ, Karamatic R et al (2006) High prevalence of sessile serrated adenomas with BRAF mutations: a prospective study of patients undergoing colonoscopy. Gastroenterology 131:1400–1407

    Article  PubMed  CAS  Google Scholar 

  28. Takahashi T, Nosho K, Yamamoto H et al (2007) Flat-type colorectal advanced adenomas (laterally spreading tumors) have different genetic and epigenetic alterations from protruded-type advanced adenomas. Mod Pathol 20:139–147

    Article  PubMed  CAS  Google Scholar 

  29. Vaahtomeri K, Mäkelä TP (2011) Molecular mechanisms of tumor suppression by LKB1. FEBS Lett 585:944–951

    Article  PubMed  CAS  Google Scholar 

  30. Zeki SS, Graham TA, Wright NA (2011) Stem cells and their implications for colorectal cancer. Nat Rev Gastroenterol Hepatol 8:90–100

    Article  PubMed  Google Scholar 

Download references

Danksagung

Der Autor dankt Herrn Prof. Dr. Helmut Neumann, Erlangen, für die Überlassung von Abb. 2.

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. Institut für Pathologie, Medizinische Universität Graz, Auenbruggerplatz 25, 8036, Graz, Österreich

    C. Langner

Authors
  1. C. Langner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Langner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Langner, C. Nichtserratierte Vorläuferläsionen von Tumoren des Dickdarms. Pathologe 32 (Suppl 2), 206 (2011). https://doi.org/10.1007/s00292-011-1495-2

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s00292-011-1495-2

Schlüsselworte

Keywords

Search

Navigation