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ID 117614
Title Alternative
鋸歯状ポリポーシス症候群におけるadenoma-carcinoma pathwayによる発癌
Adenoma-cancer pathway in SPS
Author
Kagemoto, Kaizo Tokushima University
Kawaguchi, Tomoyuki Tokushima University
Sonoda, Tomoko Sapporo Medical University
Keywords
serrated polyposis syndrome
colorectal cancer
adenoma
sessile serrated lesion
adenoma–carcinoma pathway
serrated-neoplasia pathway
Content Type
Thesis or Dissertation
Description
Background: Although serrated polyposis syndrome (SPS) is associated with an increased colorectal cancer (CRC) risk, the carcinogenic mechanisms remain unknown. We investigated clinicopathological characteristics and genetic abnormalities in colorectal polyps and CRC to elucidate carcinogenic mechanisms in SPS.
Methods: We retrospectively analyzed clinicopathological features of colorectal polyps in 44 SPS patients, and examined mutations of genes including APC, RAS, BRAF, and TP53, and microsatellite instability (MSI) in CRC tissues.
Results: Of the 44 patients, 25 (56%) fulfilled WHO criterion 1, 11 (25%) fulfilled criterion 2, and 8 (18%) fulfilled both. A total of 956 polyps were observed; 642 (67%) hyperplastic polyps (HP), 204 (21%) sessile serrated lesions (SSL), 10 (1%) traditional serrated adenoma (TSA), and 100 (11%) adenomas. The median numbers of polyps (/patient) were 10.5 (IQR 2.75-23) HPs, 4.0 (2.0-6.0) SSLs, 0 (0-0) TSA, and 1 (0-3.3) adenoma. SSL and HP located preferentially in the proximal and distal colon respectively. Twenty-two CRCs were found in 18 patients. Based on the histological coexistence of SSL/TSA, BRAF mutation and MSI, 5 CRCs (26%) were classified as serrated-neoplasia pathway. Conversely, based on the coexistence of adenoma, APC/RAS and TP53 mutations, 11 CRCs (58%) were classified as adenoma-carcinoma pathway. The remaining 3 were unclassifiable. Most CRCs through adenoma-carcinoma pathway were located in the left-side colorectum and patients bearing those met criterion 2, characterized by many HP and advanced adenomas. Adenoma was a significant risk factor for CRC.
Conclusions: Our results suggest that more than half of the CRCs, particularly those in the left-side colorectum, developed through the adenoma-carcinoma pathway in SPS patients. Adenoma was a risk factor for CRCs, suggesting its importance in colorectal carcinogenesis.
Journal Title
Journal of Gastroenterology
ISSN
14355922
09441174
NCID
AA11627089
AA10988015
Publisher
Springer|Japanese Society of Gastroenterology
Volume
57
Issue
4
Start Page
286
End Page
299
Published Date
2022-02-23
Remark
内容要旨・審査要旨・論文本文の公開
本論文は,著者Fumika Nakamuraの学位論文として提出され,学位審査・授与の対象となっている。
Rights
This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Natureʼs AM terms of use (https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms), but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00535-022-01858-8
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3659号
Diploma Number
甲医第1541号
Granted Date
2022-09-22
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences