Molecular and clinicopathological features of appendiceal mucinous neoplasms
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ORIGINAL ARTICLE
Molecular and clinicopathological features of appendiceal mucinous neoplasms Yuka Yanai 1 & Tsuyoshi Saito 1,2 & Takuo Hayashi 1 & Yoichi Akazawa 3 & Noboru Yatagai 3 & Sho Tsuyama 1 & Shigeki Tomita 4 & Shu Hirai 5 & Kanako Ogura 6 & Toshiharu Matsumoto 6 & Ryo Wada 7 & Takashi Yao 1 Received: 10 December 2019 / Revised: 27 July 2020 / Accepted: 10 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Appendiceal mucinous tumors (AMTs) include low-grade mucinous appendiceal neoplasms (LAMNs), high-grade mucinous appendiceal neoplasms (HAMNs), and mucinous adenocarcinomas (MACs). We collected 51 AMT samples (LAMN: 34, HAMN: 8, MAC: 9). Three of the eight HAMN cases contained LAMN components, and four out of nine MAC cases contained LAMN and/or HAMN components within the tumor. A next-generation sequencing (NGS) cancer hotspot panel was used to analyze 11 pure LAMN, 4 HAMN, and 3 MAC cases. The results revealed KRAS and GNAS as the most frequently mutated genes. Sanger sequencing was then performed to detect KRAS, GNAS, and TP53 mutations in the remaining 31 cases and RNF43 mutations in all cases. KRAS/GNAS and TP53 mutations occurred exclusively in pure LAMNs; however, five LAMN cases had mutations in both KRAS and GNAS. RNF43 mutations almost exclusively occurred with KRAS/GNAS mutations in pure LAMNs. In MAC and HAMN, KRAS/GNAS mutation status was nearly preserved between lower-grade areas. Most of the detected RNF43 mutations was missense type. RNF43 mutations were detected in both components of MAC with lower-grade area; however, RNF43 mutations detected in these two lesions were entirely different. RNF43 mutations were detected in only one of the eight HAMN patients, which was the sole case without pseudomyxoma peritonei (PMP). None of the four MAC patients with RNF43 mutation showed PMP. These findings suggest that RNF43 mutations occur at a later stage of MAC development and do not associate with PMP. Furthermore, a gradual transition from LAMN to MAC via HAMN could be considered. Keywords Appendiceal mucinous tumor . Low-grade appendiceal mucinous neoplasm . Mucinous adenocarcinoma . KRAS . GNAS . TP53 . RNF43 . Next-generation sequencing
Abbreviations AMT Appendiceal mucinous tumor FFPE Formalin-fixed paraffin-embedded HAMN High-grade appendiceal mucinous neoplasm
IHC LAMN LOH MAC
Immunohistochemistry Low-grade appendiceal mucinous neoplasm Loss of heterozygosity Mucinous adenocarcinoma
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00428-020-02906-5) contains supplementary material, which is available to authorized users. * Tsuyoshi Saito [email protected] 1
Department of Human Pathology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
2
Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan
3
Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan
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