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

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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.

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Acknowledgments

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 (www.editage.jp) for English language editing.

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Authors and Affiliations

  1. Division of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852 8501, Japan

    Hideo Wada & Takeshi Nagayasu

  2. 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

    Hideo Wada, Katsuya Matsuda, Nozomi Ueki & Masahiro Nakashima

  3. Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852 8501, Japan

    Yuko Akazawa

  4. Medical Student Research Programme, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan

    Yuka Yamaguchi

  5. Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan

    Shiro Miura & Masahiro Nakashima

  6. Department of Human Genetics, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan

    Akira Kinoshita & Koh-ichiro Yoshiura

  7. Biostatic section, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan

    Hisayoshi Kondo

  8. Department of Pathology, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, Nagasaki, 856 8562, Japan

    Masahiro Ito

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  1. Hideo Wada
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  9. Hisayoshi Kondo
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  11. Takeshi Nagayasu
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  12. Masahiro Nakashima
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Corresponding author

Correspondence to Masahiro Nakashima.

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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 (http://www-sdc.med.nagasaki-u.ac.jp/pathology/index.html) following the guidelines of the Ethical Committee’s official disclosure system.

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The authors declare that they have no conflict of interest.

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Wada, H., Matsuda, K., Akazawa, Y. et al. Expression of Somatostatin Receptor Type 2A and PTEN in Neuroendocrine Neoplasms Is Associated with Tumor Grade but Not with Site of Origin. Endocr Pathol 27, 179–187 (2016). https://doi.org/10.1007/s12022-016-9436-5

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  • DOI: https://doi.org/10.1007/s12022-016-9436-5

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