DNA Content Analysis of Colorectal Serrated Lesions Detects an Aneuploid Subset of Inflammatory Bowel Disease-Associated Serrated Epithelial Change and Traditional Serrated Adenomas.

Authors：Choi Won Tak; Wen Kwun Wah; Rabinovitch Peter S; Huang Danning; Mattis Aras N; Gill Ryan M

Source：Histopathology, 2018.

DOI：10.1111/his.13652

• Aneuploidy
• colorectal cancer
• dysplasia
• serrated lesion

AIMS: Serrated lesions (SLs), including sessile serrated adenoma (SSA) and traditional serrated adenoma (TSA), are important premalignant lesions for colorectal cancer (CRC). Although a small subset of SLs are known to harbor TP53 mutations and Wnt/beta-catenin pathway activation, suggesting that they may develop dysplasia or CRC via a 'chromosomal instability (CIN)-like' pathway, it is unclear if aneuploidy (characteristic of conventional adenoma) ever develops in SLs and is associated with development of dysplasia or CRC, in this context. METHODS AND RESULTS: DNA flow cytometry was performed on 31 inflammatory bowel disease (IBD)-associated SLs without dysplasia (including 10 non-targeted 'serrated epithelial change' (SEC), 14 SSAs, and 7 hyperplastic polyps [HPs]) as well as 48 dysplastic SSAs and TSAs. One (10%) of 10 SEC cases demonstrated aneuploidy and subsequently developed HGD within 4 months, whereas the remaining SEC cases showed normal DNA content without evidence of dysplasia or CRC on follow-up. One (3.3%) of 30 TSAs without HGD and 2 (66.7%) of 3 TSAs with HGD also showed aneuploidy, but no patient developed CRC. By contrast, all SSAs (with or without dysplasia) and HPs showed normal DNA content, but 4 SSA cases still developed dysplasia or CRC on follow-up. CONCLUSIONS: Unlike SSAs and HPs, a small subset of SEC and TSA cases demonstrated aneuploidy, suggesting that they can develop neoplasia via the CIN pathway. DNA content analysis of a larger number of SEC cases, with adequate follow-up, may allow for a more precise determination of aneuploidy incidence and neoplasia risk.

• Institution
  university of california; the University of Washington; SUNY Upstate Medical University; University of washington