Skip to main content
SpringerLink
Log in

Markerprofile für das Fernmetastasierungsrisiko des Dickdarmkarzinoms

Prognostic marker profiles for risk of distant metastases in colorectal cancer

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

Zusammenfassung

Prognostische Marker, die mit dem Auftreten von Fernmetastasen beim Dickdarmkarzinom korrelieren, sind von großer klinischer Bedeutung. In den letzten Jahren konnte gezeigt werden, dass sporadische Dickdarmkarzinome mit einer Mikrosatelliteninstabilität (MSI) ein äußerst niedriges Fernmetastasierungsrisiko aufweisen, wobei das medulläre Karzinom hierfür einen morphologischen Prototyp darstellt. In der aktuellen WHO-Klassifikation werden morphologische Varianten des Dickdarmkarzinoms, wie das muzinöse, das siegelringzellige, das serratierte, das kribriform-komedoartige und das solid-undifferenzierte Karzinom bereits anhand ihres Mikrosatellitenstatus graduiert. Neue Daten zeigen, dass die BRAF-Mutation eine ambivalente prognostische Rolle spielt. Abhängig vom Mikrosatellitenstatus indiziert eine BRAF-Mutation in Kombination mit MSI eine sehr gute Prognose, während die BRAF-Mutation in Kombination mit Mikrosatellitenstabilität eine sehr schlechte Prognose anzeigt. Als Marker für ein hohes Fernmetastasierungsrisiko können, basierend auf dem Konzept der migrierenden Stammzellen, kombinierte hohe Expressionen von CD133 und nukleärem β-Catenin dienen. In Verbindung mit hMLH1 lässt sich hier ein immunhistochemischer Algorithmus definieren, der eine Unterscheidung von Dickdarmkarzinomen mit sehr niedrigem und sehr hohem Fernmetastasierungsrisiko ermöglicht.

Abstract

In colorectal cancer (CRC) prognostic markers correlating with distant metastasis are of high clinical value. In recent years it could be demonstrated that sporadic CRC with microsatellite instability (MSI) exhibits a very low risk for distant spread. Within this group the medullary subtype represents a morphological prototype. In the new WHO classification other morphological variants, such as mucinous, signet ring cell, serrated, cribriform comedo type and solid-undifferentiated forms are graded according to their microsatellite status. The clinical value of BRAF mutations is also dependent on the microsatellite status. Recent data have shown an ambivalent prognostic impact of BRAF mutations. A BRAF mutation in combination with MSI is associated with a good prognosis, whereas a BRAF mutation in the background of microsatellite stability (MSS) indicates a very poor outcome. Based on the concept of migrating stem cells, combined high scores of CD133 and nuclear β-catenin expression can be additionally used as markers for a high risk of distant metastasis. Hence, an immunohistochemical algorithm can be defined by the combination of three markers (hMLH1, CD133 and β-catenin) which allows CRC with either a very high or a very low risk of distant spread to be identified.

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

Literatur

  1. Bennecke M, Kriegl L, Bajbouj M et al (2010) Ink4a/Arf and oncogene-induced senescence prevent tumor progression during alternative colorectal tumorigenesis. Cancer Cell 18:135–146

    Article  PubMed  CAS  Google Scholar 

  2. Bosman FT, Carneiro F, Hruban RH, Theise ND (Hrsg) (2010) WHO classification of tumours of the digestive system. IARC, Lyon

  3. Brabletz T, Jung A, Spaderna S et al (2005) Opinion: migrating cancer stem cells – an integrated concept of malignant tumour progression. Nat Rev Cancer 5:744–749

    Article  PubMed  CAS  Google Scholar 

  4. Clark-Langone KM, Sangli C, Krishnakumar J et al (2010) Translating tumor biology into personalized treatment planning: analytical performance characteristics of the Oncotype DX Colon Cancer Assay. BMC Cancer 10:691

    Article  PubMed  CAS  Google Scholar 

  5. Haddad R, Ogilvie RT, Croitoru M et al (2004) Microsatellite instability as a prognostic factor in resected colorectal cancer liver metastases. Ann Surg Oncol 11:977–982

    Article  PubMed  Google Scholar 

  6. Horst D, Kriegl L, Engel J et al (2009) CD133 and nuclear beta-catenin: the marker combination to detect high risk cases of low stage colorectal cancer. Eur J Cancer 45:2034–2040

    Article  PubMed  CAS  Google Scholar 

  7. Horst D, Kriegl L, Engel J et al (2008) CD133 expression is an independent prognostic marker for low survival in colorectal cancer. Br J Cancer 99:1285–1289

    Article  PubMed  CAS  Google Scholar 

  8. Horst D, Scheel SK, Liebmann S et al (2009) The cancer stem cell marker CD133 has high prognostic impact but unknown functional relevance for the metastasis of human colon cancer. J Pathol 219:427–434

    Article  PubMed  CAS  Google Scholar 

  9. Jass JR (2007) Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology 50:113–130

    Article  PubMed  CAS  Google Scholar 

  10. Kirchner T, Reu S (2008) Development of molecular-pathologic entities of colorectal cancer. Pathologe 29(Suppl 2):264–269

    Article  PubMed  Google Scholar 

  11. Kriegl L, Neumann J, Vieth M et al (2011) Up and downregulation of p16(Ink4a) expression in BRAF-mutated polyps/adenomas indicates a senescence barrier in the serrated route to colon cancer. Mod Pathol 24:1015–1022

    Article  PubMed  CAS  Google Scholar 

  12. Lanza G, Gafa R, Matteuzzi M et al (1999) Medullary-type poorly differentiated adenocarcinoma of the large bowel: a distinct clinicopathologic entity characterized by microsatellite instability and improved survival. J Clin Oncol 17:2429–2438

    PubMed  CAS  Google Scholar 

  13. Lee S, Cho NY, Choi M et al (2008) Clinicopathological features of CpG island methylator phenotype-positive colorectal cancer and its adverse prognosis in relation to KRAS/BRAF mutation. Pathol Int 58:104–113

    Article  PubMed  CAS  Google Scholar 

  14. Leggett B, Whitehall V (2010) Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology 138:2088–2100

    Article  PubMed  CAS  Google Scholar 

  15. Lindor NM, Burgart LJ, Leontovich O et al (2002) Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol 20:1043–1048

    Article  PubMed  CAS  Google Scholar 

  16. Malesci A, Laghi L, Bianchi P et al (2007) Reduced likelihood of metastases in patients with microsatellite-unstable colorectal cancer. Clin Cancer Res 13:3831–3839

    Article  PubMed  CAS  Google Scholar 

  17. Neumann J, Horst D, Kriegl L et al (2011) A simple immunohistochemical algorithm predicts the risk of distant metastases in right-sided colon cancer. Histopathology [Epub ahead of print]

  18. Roth AD, Tejpar S, Delorenzi M et al (2010) Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60–00 trial. J Clin Oncol 28:466–474

    Article  PubMed  CAS  Google Scholar 

  19. Samowitz WS, Sweeney C, Herrick J et al (2005) Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. Cancer Res 65:6063–6069

    Article  PubMed  CAS  Google Scholar 

  20. Shia J (2008) Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part I. The utility of immunohistochemistry. J Mol Diagn 10:293–300

    Article  PubMed  Google Scholar 

  21. Shia J, Klimstra DS, Nafa K et al (2005) Value of immunohistochemical detection of DNA mismatch repair proteins in predicting germline mutation in hereditary colorectal neoplasms. Am J Surg Pathol 29:96–104

    Article  PubMed  Google Scholar 

  22. Stone JG, Robertson D, Houlston RS (2001) Immunohistochemistry for MSH2 and MHL1: a method for identifying mismatch repair deficient colorectal cancer. J Clin Pathol 54:484–487

    Article  PubMed  CAS  Google Scholar 

  23. Tejpar S, Bertagnolli M, Bosman F et al (2010) Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery. Oncologist 15:390–404

    Article  PubMed  CAS  Google Scholar 

  24. Walther A, Johnstone E, Swanton C et al (2009) Genetic prognostic and predictive markers in colorectal cancer. Nat Rev Cancer 9:489–499

    Article  PubMed  CAS  Google Scholar 

  25. Webber EM, Lin JS, Whitlock EP (2010) Oncotype DX tumor gene expression profiling in stage II colon cancer. Application: prognostic, risk prediction. PLoS Curr 2 pii: RRN1177

    Article  Google Scholar 

  26. Wick MR, Vitsky JL, Ritter JH et al (2005) Sporadic medullary carcinoma of the colon: a clinicopathologic comparison with nonhereditary poorly differentiated enteric-type adenocarcinoma and neuroendocrine colorectal carcinoma. Am J Clin Pathol 123:56–65

    Article  PubMed  Google Scholar 

  27. Winn B, Tavares R, Fanion J et al (2009) Differentiating the undifferentiated: immunohistochemical profile of medullary carcinoma of the colon with an emphasis on intestinal differentiation. Hum Pathol 40:398–404

    Article  PubMed  CAS  Google Scholar 

  28. Zlobec I, Lugli A (2008) Prognostic and predictive factors in colorectal cancer. J Clin Pathol 61:561–569

    PubMed  CAS  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. Pathologisches Institut, Ludwig-Maximilians-Universität München, Thalkirchner Str. 36, 80337, München, Deutschland

    J. Neumann, S. Reu & T. Kirchner

Authors
  1. J. Neumann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Reu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Kirchner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Neumann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Neumann, J., Reu, S. & Kirchner, T. Markerprofile für das Fernmetastasierungsrisiko des Dickdarmkarzinoms. Pathologe 33, 39–44 (2012). https://doi.org/10.1007/s00292-011-1543-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00292-011-1543-y

Schlüsselwörter

Keywords

Search

Navigation