Adenoma-cancer pathway in SPS
Nakamura, Fumika Tokushima University Tokushima University Educator and Researcher Directory
Sato, Yasushi Tokushima University Tokushima University Educator and Researcher Directory
Okamoto, Koichi Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Fujino, Yasuteru Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Mitsui, Yasuhiro Tokushima University Tokushima University Educator and Researcher Directory
Kagemoto, Kaizo Tokushima University
Kawaguchi, Tomoyuki Tokushima University
Miyamoto, Hiroshi Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Sonoda, Tomoko Sapporo Medical University
Tsuneyama, Koichi Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
serrated polyposis syndrome
sessile serrated lesion
Thesis or Dissertation
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 of Gastroenterology
Springer|Japanese Society of Gastroenterology
|DOI (Published Version)|
|URL ( Publisher's Version )|
k3659_abstract.pdf 115 KB
k3659_review.pdf 120 KB
k3659_fulltext.pdf 2.19 MB
|MEXT report number||
Doctor of Medical Science