Endocrine Pathology

, Volume 27, Issue 3, pp 179–187 | Cite as

Expression of Somatostatin Receptor Type 2A and PTEN in Neuroendocrine Neoplasms Is Associated with Tumor Grade but Not with Site of Origin

  • Hideo Wada
  • Katsuya Matsuda
  • Yuko Akazawa
  • Yuka Yamaguchi
  • Shiro Miura
  • Nozomi Ueki
  • Akira Kinoshita
  • Koh-ichiro Yoshiura
  • Hisayoshi Kondo
  • Masahiro Ito
  • Takeshi Nagayasu
  • Masahiro NakashimaEmail author


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.


Neuroendocrine neoplasm PTEN SSTR2A p53 FISH ddPCR 



This work was supported in part by a collaborative research grant from the Atomic Bomb Disease Institute, Nagasaki University. We would like to thank Editage ( for English language editing.

Compliance with Ethical Standards

The present study was an unlinkable anonymized study strictly following the principles established in the Declaration of Helsinki and was approved by the Committee for Ethical Issues of Nagasaki University Graduate School of Biomedical Sciences (Date of approval; Aug. 20, 2015, Protocol No. 15682035). As this was a retrospective research study involving minimal risk to the participants, detailed information of the research was released to the public on the institution’s homepage ( following the guidelines of the Ethical Committee’s official disclosure system.

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Hideo Wada
    • 1
    • 2
  • Katsuya Matsuda
    • 2
  • Yuko Akazawa
    • 3
  • Yuka Yamaguchi
    • 4
  • Shiro Miura
    • 5
  • Nozomi Ueki
    • 2
  • Akira Kinoshita
    • 6
  • Koh-ichiro Yoshiura
    • 6
  • Hisayoshi Kondo
    • 7
  • Masahiro Ito
    • 8
  • Takeshi Nagayasu
    • 1
  • Masahiro Nakashima
    • 2
    • 5
    Email author
  1. 1.Division of Surgical OncologyNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  2. 2.Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease InstituteNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  3. 3.Department of Gastroenterology and HepatologyNagasaki University HospitalNagasakiJapan
  4. 4.Medical Student Research ProgrammeNagasaki University School of MedicineNagasakiJapan
  5. 5.Tissue and Histopathology Section, Atomic Bomb Disease InstituteNagasaki UniversityNagasakiJapan
  6. 6.Department of Human Genetics, Atomic Bomb Disease InstituteNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  7. 7.Biostatic section, Atomic Bomb Disease InstituteNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  8. 8.Department of PathologyNational Hospital Organization Nagasaki Medical CenterNagasakiJapan

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