Colorectal Serrated Lesions: A Current View on Clinical, Morphological, Molecular, and Genetic Diagnostic Criteria

Abstract

Objective: Serrated colorectal lesions are a group of colonic lesions with a serrated (saw-tooth) profile of the surface epithelium and crypts and peculiar molecular and genetic developmental mechanisms that are incompletely understood. These formations cause concern due to their premalignant potential. Aim: The review is dedicated to serrated lesions of the colon and appendix. We focused on modern classification, its role in carcinogenesis, and new approaches to morphological diagnosis. Methods: A literature search was performed using PubMed, Scopus, ResearchGate, Google, MEDLINE, and ScienceDirect databases to find studies of serrated colorectal lesions related cancer published between 2000 and 2020 that address epidemiological of risk factors, underlying pathophysiological mechanism and enable our review of these factors as well molecular, genetics, and structural patterns. Results: Serrated colorectal lesions take one-third of all benign neoplasms of the colon in the pathologist’s practice. The active study of serrated lesions began in the 1900s. Terminology and diagnostic criteria were changed in the updated classification in 2019. Morphological criteria, immunohistochemical and molecular profile, endoscopic and clinical characteristics are reviewed. Conclusion: Significant efforts were made to improve our understanding and diagnostic criteria of serrated polyps of the colorectum. Very little change has occurred since the original morphologic description of preneoplastic serrated lesions in the early 2000s. More research remains needed to develop more definitive immunophenotypic and molecular biomarkers to distinguish between non-neoplastic and neoplastic serrated lesions.

DNA methylation modulates epigenetic regulation in colorectal cancer diagnosis, prognosis and precision medicine

“…Additionally, there were notable differences in CXCR4 protein expression between microsatellite instable (MSI) and microsatellite stable (MSS) tumor cell lines. Although no differential methylation was detected in CXCR4 compared to adjacent mucosa, the accumulation of 5hmC was observed in the CXCR4 gene bodies in CRC [12,13]. Further studies are warranted to understand the mechanism of CXCR4 promoter hypermethylation and its role in CRC.…”

“…When considering polyps, it is imperative to address serrated polyps, constituting approximately 15% to 30% of all CRC cases [ 14 ]. Serrated polyps are primarily distinguished by BRAF and/or KRAS genetic mutations, coupled with epigenetic alterations in the CpG island methylator phenotype (CIMP), collaborating to initiate and propel malignant transformation from normal colon mucosa to polyps and ultimately to CRC [ 15 ].…”