Terminology, Molecular Features, Epidemiology, and Management of Serrated Colorectal Neoplasia

Abstract

In addition to the adenoma to carcinoma sequence, colorectal carcinogenesis can occur via the serrated pathway. Studies have focused on clarification of categories and molecular features of serrated polyps, as well as endoscopic detection and risk assessment. Guidelines from the World Health Organization propose assigning serrated polyps to categories of hyperplastic polyps, traditional serrated adenomas, and sessile serrated lesions (SSLs). Traditional serrated adenomas and SSLs are precursors to colorectal cancer. The serrated pathway is characterized by mutations in RAS and RAF, disruptions to the Wnt signaling pathway, and widespread methylation of CpG islands. Epidemiology studies of serrated polyps have been hampered by inconsistencies in terminology and reporting, but the prevalence of serrated class polyps is 20%-40% in average-risk individuals; most serrated polyps detected are hyperplastic. SSLs, the most common premalignant serrated subtype, and are found in up to 15% of average-risk patients by highdetecting endoscopists. Variations in rate of endoscopic detection of serrated polyps indicate the need for careful examination, with adequate bowel preparation and sufficient withdrawal times. Risk factors for SSLs include white race, family history of colorectal cancer, smoking, and alcohol intake. Patients with serrated polyps, particularly SSLs and traditional serrated adenomas, have an increased risk of synchronous and metachronous advanced neoplasia. Surveillance guidelines vary among countries, but SSLs and proximal hyperplastic polyps require special attention in assignment of surveillance interval-especially in light of concerns regarding incomplete detection and resection.

Polyp Detection Rate as a Surrogate for Adenoma and Sessile Serrated Adenoma/Polyp Detection Rates

“…The literature as well as our cohort support the belief of a higher SSA/P prevalence is present in western countries [28][29][30][31][32]. From the 701 diminutive RS polyps with confirmed tissue on histology, 305 were neoplastic (43.5%).…”

Role of RASA1 in cancer: A review and update (Review)

“…The incidence of colorectal cancer (CRC) is rising and is predicted to increase to 2.5 million new cases by 2035 and is ranked third among malignant tumours across the world and second in some developing areas ( 67 , 68 ). Colorectal specimens including 468 colorectal tumour samples from a large personalised medicine initiative and 17 paired primary-metastatic and 2 metastatic-metastatic specimens from 18 CRC patients were analysed by next-generation sequencing to reveal the presence of RASA1 mutations ( 69 ).…”

Biology and Therapeutic Targets of Colorectal Serrated Adenocarcinoma; Clues for a Histologically Based Treatment against an Aggressive Tumor

“…In addition to this higher abundance of synchronous carcinoma compared to CC, distant polyps present in surgical resections containing SAC frequently show serrated morphology, thus suggesting a bystander effect or individual predisposition for serrated carcinogenesis [11]. At this point it, is noteworthy that smoking and alcohol abuse have been associated with the development of the serrated carcinogenesis pathway [14][15][16], as well as the presence of Fusobacterium nucleatum in the patient's feces [17].…”