title: Expression of Somatostatin Receptor Type 2A and PTEN in Neuroendocrine Neoplasms Is Associated with Tumor Grade but Not with Site of Origin.
abstract: Neuroendocrine neoplasms (NENs) are derived from endocrine cells in various organs and share common morphological features. This study aimed to clarify whether NENs of different organs are comparable at the molecular pathologic level. We retrospectively collected 99 cases of NENs from gastro-entero-pancreatic, lung, and other organs and reclassified these according to identical criteria. Grade, site, and molecular expression profile including NE markers, Ki-67, p53, somatostatin receptor type 2A (SSTR2A), and phosphatase and tensin homolog (PTEN) were compared. PTEN immunoreactivity was also compared with genomic copy number by fluorescence in situ hybridization (FISH) and droplet digital polymerase chain reaction (ddPCR). No significant differences were observed in the immunoreactivities of NE markers, p53, SSTR2A, or PTEN expression in NENs between the different organ sites. PTEN and p53 functional inactivation along with the loss of membranous SSTR2A expression appeared to be commonly involved in high-grade NEN. FISH results were significantly correlated with the level of PTEN immunoreactivity and with the findings of ddPCR analyses. The demonstration that these tumors are comparable at the molecular level will likely contribute to the broadening of therapeutic options such as the use of somatostatin analogues and mTOR inhibitors against NENs regardless of the affected organ, whereas molecular characterization of tumor grade will be useful for determining treatment strategy.
authors.affiliation: Division of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852 8501, Japan.|Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Wada
authors.affiliation: Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852 8501, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Akazawa
authors.affiliation: Medical Student Research Programme, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Miura
authors.affiliation: Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Ueki
authors.affiliation: Department of Human Genetics, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kinoshita
authors.affiliation: Department of Human Genetics, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan.
authors.forename: Koh-Ichiro
authors.initials: K
authors.lastname: Yoshiura
authors.affiliation: Biostatic section, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan.
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Kondo
authors.affiliation: Department of Pathology, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, Nagasaki, 856 8562, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ito
authors.affiliation: Division of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852 8501, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagayasu
authors.affiliation: Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan. moemoe@nagasaki-u.ac.jp.|Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan. moemoe@nagasaki-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakashima
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D017481:Receptors, Somatostatin / Q000096:biosynthesis*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D017481:Receptors, Somatostatin; C574734:SSTR2 protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: FISH; Neuroendocrine neoplasm; PTEN; SSTR2A; ddPCR; p53