Traditional serrated adenoma has two distinct genetic pathways for molecular tumorigenesis with potential neoplastic pro
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ORIGINAL ARTICLE—ALIMENTARY TRACT
Traditional serrated adenoma has two distinct genetic pathways for molecular tumorigenesis with potential neoplastic progression Yoshihito Tanaka1 • Makoto Eizuka1 • Noriyuki Uesugi1 • Keisuke Kawasaki2 Hiroo Yamano3 • Hiromu Suzuki4 • Takayuki Matsumoto2 • Tamotsu Sugai1
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Received: 9 January 2020 / Accepted: 29 May 2020 Ó The Author(s) 2020
Abstract Background Recent studies have shown that traditional serrated adenoma (TSA) can be classified into BRAF and KRAS subtypes. Here, we examined the clinicopathological and molecular findings of 73 TSAs. Materials and methods TSAs were subclassified into BRAF type (46 cases, type A) and KRAS type (27 cases, type B) and divided into polyp head (TSA component) and base (precursor component [PC]) to identify pathological and molecular differences between the two components. BRAF and KRAS mutations, microsatellite instability (MSI), and DNA methylation status of the TSA component and PC were analyzed. In addition, immunohistochemical expressions of annexin A10, MUC2, MUC5AC, MUC6,
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00535-020-01697-5) contains supplementary material, which is available to authorized users. & Tamotsu Sugai [email protected] 1
Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 2-1-1, Idai-dori, Yahaba-cho, Shiwa-gun, Iwate 028-3695, Japan
2
Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 21-1, Idai-dori, Yahaba-cho, Shiwa-gun, Iwate 028-3695, Japan
3
Department of Gastroenterology and Hepatology, School of Medicine, Sapporo Medical University, South-1 West-17, Chuo-ku, Sapporo 060-8556, Japan
4
Department of Molecular Biology, School of Medicine, Sapporo Medical University, South-1 West-17, Chuo-ku, Sapporo 060-8556, Japan
and CD10 were also examined. Finally, we compared endoscopic findings with histological features. Results We classified type As into 31 type A1s with mutation of the corresponding PC (42.5%) and 15 type A2s without mutation of the PC (20.5%). None of the corresponding PCs without KRAS mutation were observed in type Bs. MSI was not detected in the TSAs examined. There were significant differences in the frequency of annexin A10 and MUC5AC expression between the three subtypes. Furthermore, we compared the TSA component with the corresponding PC to identify the progression mechanism between the two components. Methylation status played an important role in the progression of type A1 from the corresponding PC, unlike type A2 and type B. Finally, specific endoscopic findings were well correlated with distinct histological findings. Conclusion TSAs were heterogeneous tumors with two or three pathways to neoplastic progression. Keywords Annexin A10 BRAF mutation KRAS mutation DNA methylation Traditional serrated adenoma Abbreviations MSS Microsatellite stable MSI Microsatellite instability TSA Traditional serrated adenoma SSL Sess
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