Polyps and colorectal cancer in serrated polyposis syndrome: contribution of the classical adenoma-carcinoma and serrated neoplasia pathways

• Published in: Clinical and translational gastroenterology Vol. 14; no. 8; p. e00611
• Main Authors: van Toledo, David E F W M, IJspeert, Joep E G, Boersma, Hannah, Musler, Alex R, Bleijenberg, Arne G C, Dekker, Evelien, van Noesel, Carel J M
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer 26.06.2023
• Subjects: Colon
• ISSN: 2155-384X; 2155-384X
• DOI: 10.14309/ctg.0000000000000611

Patients with serrated polyposis syndrome (SPS) have an increased risk to develop colorectal cancer (CRC). Due to an abundance of serrated polyps (SPs), these CRCs are assumed to arise mainly through the serrated neoplasia pathway rather than through the classical adenoma-carcinoma pathway. We aimed to evaluate the pathogenetic routes of CRCs in SPS patients. We collected endoscopy and pathology data on CRCs and polyps of SPS patients under treatment in our center. Our primary endpoint was the proportion of BRAFV600E mutated-CRCs, indicating serrated-pathway CRCs (sCRCs). CRCs lacking BRAFV600E most likely inferred a classical adenoma-carcinoma origin (aCRCs). We assessed patient, polyp and CRC characteristics and stratified for BRAFV600E mutation status. Thirty-five SPS patients harboured a total of 43 CRCs. Twenty-one CRCs (48.8%) carried a BRAFV600E-mutation, 10 of which lacked MLH1 straining and 17 (81%) were located in the proximal colon. Twenty-two CRCs (51.1%) did not carry a BRAFV600E-mutation and were MLH1 proficient. Of these 22 putatively aCRCs, 17 (77.3%) were located distally and one-third (36.4%) harboured a pathogenic KRAS or NRAS mutation. In patients with BRAFwt-CRCs a higher ratio of the median number of conventional adenomas versus SPs was found (3.5vs12.5) than patients with BRAFV600E-sCRCs (1vs14). Our study indicates that in SPS patients the ratio of sCRCs:aCRCs on average is fifty:fifty. This elevated sCRC:aCRC ratio in SPS patients, as compared to non-SPS patients, correlates well with the differences in the ratios of the numbers of sessile serrated lesions and conventional adenomas in SPS and non-SPS patients respectively.