Serrated pathway in colorectal carcinogenesis

Abstract

Serrated adenocarcinoma is a recently described subset of colorectal cancer (CRC), which account for about 10% of all CRCs and follows an alternative pathway in which serrated polyps replace the traditional adenoma as the precursor lesion to CRC. Serrated polyps form a heterogeneous group of colorectal lesions that includes hyperplastic polyps (HPs), sessile serrated adenoma (SSA), traditional serrated adenoma (TSA) and mixed polyps. HPs are the most common serrated polyp followed by SSA and TSA. This distinct histogenesis is believed to have a major influence in prevention strategies, patient prognosis and therapeutic impact. Genetically, serrated polyps exhibited also a distinct pattern, with KRAS and BRAF having an important contribution to its development. Two other molecular changes that have been implicated in the serrated pathway include microsatellite instability and the CpG island methylator phenotype. In the present review we will address the current knowledge of serrated polyps, clinical pathological features and will update the most recent findings of its molecular pathways. The understanding of their biology and malignancy potential is imperative to implement a surveillance approach in order to prevent colorectal cancer development.

Keywords: Serrated pathway; Colorectal carcinogenesis; Mutation; Microsatellite instability; CpG island methylator phenotype

Core tip: This paper reviews the pathologic and molecular features of serrated polyps and the serrated pathway to colorectal cancer and its clinical impact. The serrated pathway has recently emerged as the second pathway leading to colorectal cancer, and the genetic alterations occurring in this pathway are not still clarified. It’s imperative to understand the molecular profile of colorectal lesions with higher malignancy potential to implement a surveillance and screening approach in order to prevent colorectal cancer development.