| Theme | Diagnosis and Treatment of Non-ampullary Duodenal Epithelial Tumor -- Current Status and Issues | |
|---|---|---|
| Title | Molecular Features of Duodenal Carcinogenesis | |
| Publish Date | 2018/09 | |
| Author | Yohei Kojima | Department of Surgery, Kyorin University School of Medicine |
| Author | Yutaka Suzuki | Department of Surgery, Kyorin University School of Medicine |
| Author | Yoshihiro Sakamoto | Department of Surgery, Kyorin University School of Medicine |
| Author | Tadahiko Masaki | Department of Surgery, Kyorin University School of Medicine |
| Author | Toshiyuki Mori | Department of Surgery, Kyorin University School of Medicine |
| Author | Nobutsugu Abe | Department of Surgery, Kyorin University School of Medicine |
| [ Summary ] | Primary non-papillary duodenal adenocarcinoma is a rare disease; however, the pathomechanism of carcinogenesis has been elucidated. Mutations such as ERBB2 and GNAS and the ERBB/HER and Wnt signaling pathways are considered hallmarks of duodenal adenocarcinoma. Factors such as the existence of duodenal adenoma/adenocarcinoma subtypes, different bacterial flora, and bile stimulation depending upon the anatomical localization of the cancer result in different mechanisms of carcinogenesis. Whether the adenoma-carcinoma sequence is applicable to duodenal adenoma/adenocarcinoma remains unclear. In our study, adenoma/adenocarcinoma samples were classified by ductal structure based on the WHO classification. Analysis of genetic mutations in each adenoma and adenocarcinoma sample revealed that the KRAS mutation was more common in adenomas and adenocarcinomas showing high-grade dysplasia (HGD) than in adenomas showing low-grade dysplasia (LGD). The TP53 mutation was more frequent in adenocarcinomas than in adenomas showing LGD and HGD. Additionally, a few patients tend to show accumulation of mutations with an increase in the tumor grade. The possibility of an adenoma-carcinoma sequence may thus be limited in duodenal adenocarcinoma. The APC mutation is less common in adenocarcinomas. It is thus possible that other carcinogenic pathways such as de novo carcinogenesis may contribute to the development of duodenal adenocarcinoma. APC: T1556fs and STK11 mutations are very commonly observed and are considered to play an important role in the development of duodenal cancer. | |