PMID- 27256098 OWN - NLM STAT- MEDLINE DCOM- 20170301 LR - 20181113 IS - 1559-0097 (Electronic) IS - 1046-3976 (Linking) VI - 27 IP - 3 DP - 2016 Sep TI - Expression of Somatostatin Receptor Type 2A and PTEN in Neuroendocrine Neoplasms Is Associated with Tumor Grade but Not with Site of Origin. PG - 179-87 LID - 10.1007/s12022-016-9436-5 [doi] AB - 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. FAU - Wada, Hideo AU - Wada H AD - Division of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852 8501, Japan. AD - 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. FAU - Matsuda, Katsuya AU - Matsuda K AD - 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. FAU - Akazawa, Yuko AU - Akazawa Y AD - Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852 8501, Japan. FAU - Yamaguchi, Yuka AU - Yamaguchi Y AD - Medical Student Research Programme, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan. FAU - Miura, Shiro AU - Miura S AD - Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan. FAU - Ueki, Nozomi AU - Ueki N AD - 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. FAU - Kinoshita, Akira AU - Kinoshita A AD - Department of Human Genetics, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan. FAU - Yoshiura, Koh-Ichiro AU - Yoshiura K AD - Department of Human Genetics, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan. FAU - Kondo, Hisayoshi AU - Kondo H AD - Biostatic section, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan. FAU - Ito, Masahiro AU - Ito M AD - Department of Pathology, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, Nagasaki, 856 8562, Japan. FAU - Nagayasu, Takeshi AU - Nagayasu T AD - Division of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852 8501, Japan. FAU - Nakashima, Masahiro AU - Nakashima M AD - 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. AD - Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan. moemoe@nagasaki-u.ac.jp. LA - eng PT - Journal Article PL - United States TA - Endocr Pathol JT - Endocrine pathology JID - 9009288 RN - 0 (Biomarkers, Tumor) RN - 0 (Receptors, Somatostatin) RN - 0 (SSTR2 protein, human) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (PTEN protein, human) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/analysis MH - Female MH - Gene Dosage MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Neoplasm Grading MH - Neuroendocrine Tumors/*genetics/*pathology MH - PTEN Phosphohydrolase/*genetics MH - Polymerase Chain Reaction MH - Proportional Hazards Models MH - Receptors, Somatostatin/*biosynthesis MH - Retrospective Studies MH - Young Adult OTO - NOTNLM OT - FISH OT - Neuroendocrine neoplasm OT - PTEN OT - SSTR2A OT - ddPCR OT - p53 EDAT- 2016/06/04 06:00 MHDA- 2017/03/03 06:00 CRDT- 2016/06/04 06:00 PHST- 2016/06/04 06:00 [entrez] PHST- 2016/06/04 06:00 [pubmed] PHST- 2017/03/03 06:00 [medline] AID - 10.1007/s12022-016-9436-5 [pii] AID - 10.1007/s12022-016-9436-5 [doi] PST - ppublish SO - Endocr Pathol. 2016 Sep;27(3):179-87. doi: 10.1007/s12022-016-9436-5.