Intest Res.  2018 Jul;16(3):358-365. 10.5217/ir.2018.16.3.358.

Serrated neoplasia pathway as an alternative route of colorectal cancer carcinogenesis

• Kim SY
• Kim TI

• KMID: 2417647
• DOI: http://doi.org/10.5217/ir.2018.16.3.358

Abstract

In the past two decades, besides conventional adenoma pathway, a subset of colonic lesions, including hyperplastic polyps, sessile serrated adenoma/polyps, and traditional serrated adenomas have been suggested as precancerous lesions via the alternative serrated neoplasia pathway. Major molecular alterations of sessile serrated neoplasia include BRAF mutation, high CpG island methylator phenotype, and escape of cellular senescence and progression via methylation of tumor suppressor genes or mismatch repair genes. With increasing information of the morphologic and molecular features of serrated lesions, one major challenge is how to reflect this knowledge in clinical practice, such as pathologic and endoscopic diagnosis, and guidelines for treatment and surveillance.

Keyword

Serrated neoplasia; Colorectal neoplasm; Carcinogenesis; Hyperplastic polyp

MeSH Terms

Adenoma
Carcinogenesis*
Cell Aging
Colon
Colorectal Neoplasms*
CpG Islands
Diagnosis
DNA Mismatch Repair
Genes, Tumor Suppressor
Methylation
Phenotype
Polyps
United Nations

Figure

• 

  Fig. 1 Endoscopic and histologic features of sessile serrated polyps and traditional serrated adenoma. Endoscopic appearance of sessile serrated adenoma (SSA) with white light endoscopy shows smooth and indistinct surface pattern covered with mucus (A). Chromoendoscopy after indigo carmine dye spraying in SSA shows clear boundaries and characteristic pit pattern (type II-O) (B, C). Microscopic features of SSA show irregular branching and T-shaped or L-shaped basal crypt (H&E, ×400) (D). Endoscopic appearance of traditional serrated adenoma (TSA) shows protruded polypoid shape with villous surface (E), and microscopic feature of TSA shows villous serration with dysplasia (H&E, ×40) (F).

• 

  Fig. 2 Simplified models of the sessile and traditional serrated pathways. MVHP, microvesicular hyperplastic polyp; GCHP, goblet cell-rich hyperplastic polyp; IGFBT7, insulin-like growth factor-binding protein 7; SSA/P, sessile serrated adenoma/polyp; TSA, traditional serrated adenoma; TSG, tumor suppressor gene; hMLH1, human MutL homolog 1; MGMT, O-6-methylguanine-DNA methyltransferase; SSA/P-D, SSA/polyp with dysplasia; TSA-D, TSA with dysplasia; SAC, serrated adenocarcinoma; meth, methylation; MSS, microsatellite stable; CIMP-H, CpG island methylator phenotype-high; MSI, microsatellite instability; CIMP-L, CpG island methylator phenotype-low.

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