Serrated polyposis (SP) is a clinically defined syndrome characterized by the occurrence of multiple serrated
polyps in the large intestine. Individuals with SP and their relatives are at increased risk of
colorectal carcinoma (CRC). We aimed to determine the pathologic and molecular profiles of
CRCs in individuals fulfilling World Health Organization criteria for SP. A total of 45
CRCs were obtained from 38 individuals with SP (27 female and 11 male patients; median age at CRC diagnosis, 58.5 y) attending genetics clinics.
Tumor samples were pathologically reviewed, screened for somatic BRAF and KRAS mutations, and analyzed immunohistochemically for mismatch repair
protein (MMR) expression.
Tumors were spread throughout the large intestine, with 64% located in the proximal colon. Mutations in BRAF and KRAS and immunohistochemical evidence of
MMR deficiency were found in 46%, 5%, and 38%, respectively. Nearly half of
CRCs were BRAF/KRAS wild type, and these were associated with distal location (63%) and MMR proficiency (84%). Overexpression of p53 and/or evidence of β-
catenin activation were identified in 13
CRCs. Ten patients (26%) had synchronous or metachronous
CRCs. In conclusion, the majority of
CRCs arising in individuals with SP do not harbor molecular hallmarks of serrated pathway
CRCs but show a diverse range of molecular profiles. The high proportion of multiple
CRCs suggests that individuals with SP would benefit from frequent colonoscopic surveillance and from a consideration of a more extensive
colectomy at the time of CRC diagnosis.