Hyperplastic and serrated polyps of the colorectum

Area of Science:

• Gastroenterology
• Molecular Pathology
• Cancer Biology

Background:

• The serrated polyp pathway represents a distinct route of colorectal cancer (CRC) development.
• This pathway is characterized by specific molecular alterations and histopathological features.
• Understanding these pathways is crucial for accurate diagnosis and risk stratification.

Purpose of the Study:

• To delineate the molecular and histopathological characteristics of the serrated polyp pathway.
• To differentiate between distinct serrated pathways based on genetic mutations (BRAF vs. KRAS).
• To highlight the need for clinical studies on serrated neoplasia natural history and surveillance.

Main Methods:

• Histopathological analysis of serrated polyps and colorectal adenocarcinomas.
• Molecular analysis including mutation status (BRAF, KRAS) and methylation profiling (CpG-island methylation - CIMP).
• Review of existing evidence on serrated neoplasia progression.

Main Results:

• Two main serrated pathways identified: one associated with BRAF mutations, CIMP-high, and MSI; another with KRAS mutations, CIMP-low, and MSS.
• Aberrant CpG-island methylation is implicated as a driver of progression in the BRAF-mutant pathway.
• The KRAS-mutant pathway shares features with the conventional APC pathway.

Conclusions:

• Serrated polyps represent a heterogeneous group of colorectal neoplasms with distinct molecular drivers and progression patterns.
• The BRAF-mutant pathway progresses through sessile serrated adenomas and dysplastic serrated polyps to CIMP-high/MSI carcinoma.
• Further clinical research is essential to guide risk assessment and surveillance for serrated polyp precursors.