title: Unusual clinical and pathological presentation of a neuroendocrine tumor in a patient with multiple endocrine neoplasia type 1.
abstract: Neuroendocrine tumors develop in various organs in patients with multiple endocrine neoplasia type 1 (MEN1). Among those, tumors developed in upper gastrointestinal tract, thymus and bronchus have historically been called "carcinoid tumor". Occurrence of "carcinoid tumor" in other region is very rare and molecular pathogenesis of such tumors is unknown. We have experienced a patient with MEN1 who have developed an "ectopic" retroperitoneal neuroendocrine tumor. Genetic analysis of the MEN1 gene in tumor cells revealed a somatic mutation in exon 9 as well as a germline mutation in exon 10. Allele-specific amplification followed by sequence analysis revealed these two mutations exist on the different allele, indicating both alleles are functionally inactivated. Immunohistochemical staining with an anti-menin antibody revealed that wild-type menin is not expressed in tumor cells. Expression of p27(Kip1) protein is not observed in tumor cells, either. These results confirmed the inactivation of the MEN1 gene as a genetic cause of an ectopically developed neuroendocrine tumor in a patient with MEN1.
authors: Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan. aksakura@shinshu-u.ac.jp
authors: Akihiro
authors: A
authors: Sakurai
authors: Akiko
authors: A
authors: Murakami
authors: Kenji
authors: K
authors: Sano
authors: Shinya
authors: S
authors: Uchino
authors: Yoshimitsu
authors: Y
authors: Fukushima
mesh_terms: D002276:Carcinoid Tumor / Q000473:pathology*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics / Q000473:pathology*; D018358:Neuroendocrine Tumors / Q000235:genetics / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012186:Retroperitoneal Neoplasms / Q000473:pathology
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27