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  • Review Article
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Serrated neoplasia—role in colorectal carcinogenesis and clinical implications

Nature Reviews Gastroenterology & Hepatology volume 12, pages 401–409 (2015)Cite this article

Subjects

Key Points

  • Colorectal cancer (CRC) is considered a heterogeneous disease, regarding pathogenesis and clinical behaviour

  • The suggested pathogenesis of CRC from serrated polyps has led to a paradigm shift in tumour-prevention strategies

  • Common molecular alterations associated with the serrated neoplasia pathway are a mutation in the BRAF proto-oncogene and hypermethylation of CpG islands on the promoter regions of tumour suppressor genes

  • Only limited high-quality longitudinal data are available in combination with high-quality endoscopic, histopathological and molecular data, which severely restricts elucidation of this pathway

  • However, a growing body of circumstantial evidence has been accumulated, indicating that ≥15% of all CRCs arise through the serrated neoplasia pathway

Abstract

Colorectal cancer (CRC) is considered a heterogeneous disease, both regarding pathogenesis and clinical behaviour. Four decades ago, the adenoma–carcinoma pathway was presented as the main pathway towards CRC, a conclusion that was largely based on evidence from observational morphological studies. This concept was later substantiated at the genomic level. Over the past decade, evidence has been generated for alternative routes in which CRC might develop, in particular the serrated neoplasia pathway. Providing indisputable evidence for the neoplastic potential of serrated polyps has been difficult. Reasons include the absence of reliable longitudinal observations on individual serrated lesions that progress to cancer, a shortage of available animal models for serrated lesions and challenging culture conditions when generating organoids of serrated lesions for in vitro studies. However, a growing body of circumstantial evidence has been accumulated, which indicates that ≥15% of CRCs might arise through the serrated neoplasia pathway. An even larger amount of post-colonoscopy colorectal carcinomas (carcinomas occurring within the surveillance interval after a complete colonoscopy) have been suggested to originate from serrated polyps. The aim of this Review is to assess the current status of the serrated neoplasia pathway in CRC and highlight clinical implications.

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Figure 1: Representative endoscopic images of serrated lesion subtypes.
Figure 2: Representative histopathological images of serrated lesion subtypes.
Figure 3: A global and simplified model of the serrated neoplasia pathway.

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  1. Department of Gastroenterology and Hepatology, Academic Medical Centre, Meibergdreef 9, Amsterdam, 1105AZ, Netherlands

    Joep E. G. IJspeert & Evelien Dekker

  2. Laboratory for Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Academic Medical Centre, Meibergdreef 9, Amsterdam, 1105AZ, Netherlands

    Louis Vermeulen

  3. Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081HZ, Amsterdam, Netherlands

    Gerrit A. Meijer

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IJspeert, J., Vermeulen, L., Meijer, G. et al. Serrated neoplasia—role in colorectal carcinogenesis and clinical implications. Nat Rev Gastroenterol Hepatol 12, 401–409 (2015). https://doi.org/10.1038/nrgastro.2015.73

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