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- Colorectal cancer
- hyperplastic polyp
- mixed polyp
- sessile serrated adenoma
- sessile serrated polyp
- traditional serrated adenoma
- tumour biology
In the beginning, colorectal cancer (CRC) was a simple disease. It was considered a single entity, be it with different faces.1 Also, the precursor lesions of CRC were known, and the adenoma–carcinoma sequence as a model for the stepwise progression from an adenoma to an invasive CRC became a paradigm for similar lesions in other organs. Even the underlying molecular genetic alterations driving the consecutive steps of the adenoma–carcinoma were clarified.2 And so CRC was conceived to be the result of the accumulation of specific genetic mutations, at least partly due to chromosomal instability, with activated oncogenes and inactivated tumour suppressor genes causing uncontrollable cell growth. Loss of function of the APC tumour suppressor gene, the gatekeeper of the colorectum, was the initiating genetic event of adenoma formation, and familial adenomatous polyposis, caused by a germline mutation in APC, was perceived as the hereditary counterpart of sporadic CRC in the general population.3 Soon, however, the above picture became a bit more complicated, when a second form of familial CRC was discovered: the Lynch syndrome.4 The Lynch syndrome is caused by a germline defect in one of the mismatch repair genes (MLH1, MSH2, MSH6, PMS1 and PMS2) resulting in microsatellite instability. This new pathway leading to CRC was paralleled by characteristic clinicopathological features.5 Since then, through advances in endoscopical technology resulting in high-resolution views of the colonic mucosa, as well as advances in molecular genetic technology, the picture has evolved of CRC arising through a variety of pathways that can be defined at the molecular level, each accompanied by more or less specific morphology.6 The conventional adenoma no longer has the monopoly of being at the origin of …
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Competing interests None.
Provenance and peer review Commissioned; not externally peer reviewed.