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Serratierte Vorläuferläsionen

Serrated precursor lesions

Der Pathologe volume 32, Article number: 211 (2011) Cite this article

Zusammenfassung

In den vergangenen Jahren konnte der serratierte Karzinogeneseweg im Kolorektum als zweiter wichtiger Entstehungsmechanismus für kolorektale Karzinome etabliert werden. Als Vorläuferläsionen wurden dabei serratierte Polypen identifiziert, speziell das sessile serratierte Adenom (SSA) und das traditionelle serratierte Adenom (TSA). Molekulare Schlüsselveränderungen sind beim SSA aktivierende BRAF- und beim TSA KRAS-Onkogen-Mutationen sowie die epigenetische Methylierung von sog. CpG-Inseln im Bereich von Genpromotoren („CpG-island methylation phenotype“, CIMP) von Genen, die für die Zellzykluskontrolle oder die DNA-Reparatur wichtig sind. Diese Erkenntnisse haben insofern zu einem Paradigmenwechsel in der Pathologie des Gastrointestinaltrakts geführt, als nunmehr erstmals Läsionen mit rein architektonischen Alterationen ohne zytomorphologische Dysplasie (bestimmte hyperplastische Polypen, SSA) als Präkanzerosen akzeptiert wurden. Die Karzinome aus dem serratierten Karzinogeneseweg zeigen überdies – in Abhängigkeit von ihren molekularen Aberrationen – ein unterschiedliches biologisches Verhalten mit Relevanz für das klinische Management.

Abstract

The so-called serrated pathway has in recent years been well established as a second route of colorectal carcinogenesis. Sessile serrated polyps, especially sessile serrated adenomas (SSA) and traditional serrated adenomas (TSA) were identified as precursor lesions of this pathway. Activating mutations in either the BRAF (in SSAs) or the KRAS oncogene (in TSAs) have been determined as the initiating molecular alterations, followed by epigenetic methylation of CpG islands in promoter regions of genes which are implicated in cell cycle control or DNA repair. These findings have led to a paradigm shift in gastrointestinal pathology as lesions without cytological dysplasia, such as SSAs and certain forms of hyperplastic polyps, are now accepted to be precancerous lesions. In addition, carcinomas that have developed through the serrated pathway of colorectal carcinogenesis show varying biological behavior relevant for the clinical management of these tumors depending on the molecular aberrations.

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Affiliations

  1. Institut für Pathologie, Universitätsklinikum Carl Gustav Carus, TU Dresden, Fetscherstr. 74, 01307, Dresden, Deutschland

    G.B. Baretton & D.E. Aust

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  1. G.B. Baretton
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  2. D.E. Aust
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Correspondence to G.B. Baretton.

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Baretton, G., Aust, D. Serratierte Vorläuferläsionen. Pathologe 32, 211 (2011). https://doi.org/10.1007/s00292-011-1494-3

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  • DOI: https://doi.org/10.1007/s00292-011-1494-3

Schlüsselwörter

  • Kolonpolypen
  • Präkanzeröses Konditionen
  • Sessiles serratiertes Adenom
  • Traditionelles serratiertes Adenom
  • Kolorektales Karzinom

Keywords

  • Colonic polyps
  • Precancerous conditions
  • Sessile serrated adenoma
  • Traditional serrated adenoma
  • Colorectal cancer