Pathways for the development of multiple epithelial types of intraductal papillary mucinous neoplasm of the pancreas

Toshikazu Kobayashi, Yuko Omori, Yusuke Ono, Hidenori Karasaki, Yusuke Mizukami, Naohiko Makino, Fuyuhiko Motoi, Michiaki Unno, Yoshiyuki Ueno, Toru Furukawa

研究成果: Article査読

1 被引用数 (Scopus)

抄録

Background: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is categorized into four distinct types: the gastric, intestinal, pancreatobiliary, and oncocytic. Each type is associated with specific clinicopathological features. We aimed to uncover the molecular mechanisms underlying the development of these types of IPMN. Methods: We obtained 103 lesions of various types, including 49 gastric, 26 intestinal, 22 pancreatobiliary, and 6 oncocytic lesions, from 43 IPMNs, including 36 with multiple types. Comparative analysis was performed by targeted sequencing of 37 genes in different lesion types within each pancreas. Results: Gastric-type low-grade lesions were observed in all 36 tumors with multiple types, with 245 mutations identified across all samples. The average number of mutations was significantly different between different lesion grades and types: 1.88 for low-grade lesions, 2.77 for high-grade lesions, and 2.38 for invasive lesions (p = 0.0067); and 1.96 for gastric-type lesion, 2.92 for intestinal-type lesion, 2.73 for pancreatobiliary-type lesion, and 2.17 for oncocytic-type lesion (p = 0.0163). Tracing of mutations between lesions containing multiple types in the same pancreas suggested three developmental pathways, denoted as “progressive”, “divergent”, and “independent”. The progressive and divergent pathways indicate an ancestral lesion that was mostly gastric-type and low-grade may progress or diversify into lesions of other types and/or higher grades. The independent pathway suggests that some high-grade lesions of any type may develop independently. Conclusion: These findings suggest that gastric-type low-grade lesions have a risk of progression into high-grade lesions of other types. Therefore, low-grade gastric-type IPMNs should be under constant surveillance.

本文言語English
ページ(範囲)581-592
ページ数12
ジャーナルJournal of gastroenterology
56
6
DOI
出版ステータスPublished - 2021 6

ASJC Scopus subject areas

  • 消化器病学

フィンガープリント

「Pathways for the development of multiple epithelial types of intraductal papillary mucinous neoplasm of the pancreas」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル