Serrated Colorectal Neoplasia Pathway Analysis

The serrated neoplasia pathway represents an alternative multistep route to colorectal cancer that accounts for approximately 15–30% of cases. Rather than arising from conventional adenomas, serrated cancers develop from a spectrum of serrated polyps characterised by saw-tooth glandular architecture. These lesions include hyperplastic polyps, sessile serrated lesions (SSLs) and traditional serrated adenomas (TSAs). Molecularly, the pathway is driven by activating mutations in BRAF or KRAS, combined with widespread DNA methylation of promoter CpG islands (the CpG island methylator phenotype). This epigenetic silencing can inactivate key tumour suppressor genes, notably MLH1, leading to microsatellite instability and rapid progression to malignancy. Histological diversity and flat morphology make early detection challenging, underscoring the need for refined endoscopic techniques and molecular markers. Current research integrates genomic, epigenomic and immunological analyses to map the transition from normal mucosa to serrated polyp and ultimately invasive carcinoma, with the aim of improving risk stratification, surveillance guidelines and therapeutic targets on a global scale.

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Serrated Colorectal Neoplasia Pathway Analysis publication trend

The graph below shows the total number of articles in serrated colorectal neoplasia pathway analysis across all publications each year (not limited to Nature Index journals).

Technical terms

Sessile serrated lesion (SSL): A flat or minimally raised serrated polyp of the colon that can progress to colorectal cancer via dysplastic changes.

Traditional serrated adenoma (TSA): A serrated polyp subtype with villiform architecture and cytological atypia, representing a precursor to colorectal carcinoma.

CpG island methylator phenotype (CIMP): A pattern of widespread DNA methylation at gene promoter regions that silences tumour suppressor genes and contributes to serrated pathway carcinogenesis.

Microsatellite instability (MSI): A condition of genetic hypermutability resulting from defective DNA mismatch repair, often seen in serrated pathway tumours.

Dysplasia: Histological term for abnormal cell growth that indicates pre-cancerous transformation within a polyp.

References

1. Sessile serrated lesions with dysplasia: is it possible to nip them in the bud?. Journal of Gastroenterology (2023).
2. Serrated Colorectal Lesions: An Up-to-Date Review from Histological Pattern to Molecular Pathogenesis. International Journal of Molecular Sciences (2022).
3. The Molecular Hallmarks of the Serrated Pathway in Colorectal Cancer. Cancers (2019).