About Half of Cancers in Serrated Polyposis Syndrome Arise Through the Adenoma-Carcinoma Sequence

The serrated pathway of colorectal cancer (CRC) is considered to account for about 20% of all CRCs. Patients with serrated polyposis syndrome (SPS) have higher numbers of serrated polyps and increased risk of CRC, but recent evidence suggests that only about half of the cancers in SPS arise through the serrated pathway, and the remainder originates through the adenoma-carcinoma pathway rather than the serrated pathway.

In a cohort of 228 patients with SPS, there were 43 CRCs in 35 patients. About half (21/43) of the CRCs had mutations in the BRAF gene and thus were considered to have passed through the serrated pathway. The other half were wild-type BRAF mutations and passed through the adenoma-carcinoma sequence. Patients with BRAF mutations in their CRC had fewer adenomas in the colon. The ratio of serrated lesions to adenomas was 14:1 in the patients with BRAF mutations but 4:1 in the patients with wild-type BRAF mutations. BRAF-mutated lesions were largely in the proximal colon, and wild-type BRAF cancers were mostly in the distal colon.