Differential expression and tumorigenic function of neurotensin receptor 1 in neuroendocrine tumor cells. Myt1 and Ngn3 form a feed-forward expression loop to promote endocrine islet cell differentiation. Chromosomal and molecular pathway alterations in the neuroendocrine carcinoma and adenocarcinoma components of gastric mixed neuroendocrine-nonneuroendocrine neoplasm. Looking into digestive mixed neuroendocrine–nonneuroendocrine neoplasms: subtypes, prognosis, and predictive factors. Digestive System Tumors, WHO Classification of Tumors 5th Edition. In: WHO Classification of Tumors Editorial Board. Classification of neuroendocrine neoplasms fo the digestive system. Digestive system mixed neuroendocrine-non-neuroendocrine neoplasms. Mixed Adenoneuroendocrine Carcinomas (MANECs) of the gastrointestinal tract: an update. Carcinoid tumors and the mixed (composite) glandular-endocrine cell carcinomas. Hyperplasias and tumors of the disseminated endocrine (paracrine) Helle Zellen Feyrter’s of the gut with special regard of amphicrine cell proliferations (author’s transl). These data provide a foundation for further studies on the development and progression of amphicrine carcinoma. In summary, our study revealed the unique CN and mutation characteristics of gastric amphicrine carcinoma and differentiated these characteristics from those of MiNENs. An integrated KEGG pathway analysis showed that the estrogen signaling pathway was enriched in amphicrine carcinomas, which might be associated with the high morbidity of male patients. There were no specific mutation characteristics to distinguish amphicrine carcinoma from MiNEN. WES showed frequent somatic mutations of TP53 (37.5%, 3/8) and APC (25.0%, 2/8) in amphicrine carcinoma. Moreover, the CN level of C5 (complement C5) was higher in amphicrine carcinoma than in both the adenocarcinoma and the NEC component of MiNENs, suggesting that amphicrine carcinomas might benefit more from C5 inhibitors than MiNENs. The CN characteristics of gastric amphicrine carcinomas were different from those of MiNENs in hierarchical clustering analysis, suggesting that amphicrine carcinoma is a separate entity from MiNEN.
Amplifications of MYT1, NTSR1, and ZBTB46 located in this region were demonstrated by qPCR and immunohistochemistry. The most frequent high-level CN variant was a gain of 20q13.12–20q13.2, which was found in five gastric amphicrine carcinomas. In this study, we performed high-resolution copy number (CN) profiling and whole exome sequencing (WES) of formalin-fixed and paraffin-embedded (FFPE) tissues from eight gastric amphicrine carcinomas and compared the molecular features with those of the adenocarcinoma and neuroendocrine carcinoma (NEC) components of eight gastric MiNENs. Gastric amphicrine carcinoma, in which endocrine and epithelial cell features are present within the same cells, is often confused with gastric mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN).