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Different Hormonal Expression Patterns Between Primary Pancreatic Neuroendocrine Tumors and Metastatic Sites

Kimura, Hideyo MD; Ohtsuka, Takao MD, PhD; Fujimoto, Takaaki MD; Date, Kenjiro MD; Matsunaga, Taketo MD; Cases, Ana Ines MD, PhD; Abe, Atsushi MD; Mizuuchi, Yusuke MD, PhD; Miyasaka, Yoshihiro MD, PhD; Ito, Tetsuhide MD, PhD; Oda, Yoshinao MD, PhD; Nakamura, Masafumi MD, PhD; Tanaka, Masao MD, PhD, FACS

doi: 10.1097/MPA.0000000000000570
Original Articles

Objectives Pancreatic neuroendocrine tumors (PNETs) are known to have heterogeneity in terms of their ability to produce multiple hormones. The aim of this study was to evaluate the heterogeneity of PNETs from the viewpoint of hormonal expression.

Methods The expressions of 4 representative hormones, gastrin, insulin, glucagon, and somatostatin, in both primary and metastatic lesions, were analyzed by immunohistochemical staining in 20 patients with metastatic PNETs (6 gastrinomas, 1 insulinoma, 1 glucagonoma, and 12 nonfunctioning PNETs [NF-PNETs]). Metastatic sites included lymph nodes in all 20 patients and liver metastasis in 7 patients (2 gastrinomas and 5 NF-PNETs).

Results There were 6 PNETs with multiple hormone secretion (30%), and positive expression of 1 or more hormones was found in 9 of 12 patients whose primary tumors were diagnosed as NF-PNETs. The positive concordance rate of the hormonal expression pattern between primary tumors and metastatic lymph nodes and between primary tumors and hepatic metastasis were 50% and 11%, respectively. Three patients had metastatic lesions with positive hormonal expression, whereas their primary tumors were negative.

Conclusions Hormonal expressions are often different between the primary tumors and metastatic sites of PNETs.

From the *Department of Surgery and Oncology, †Department of Anatomic Pathology, and ‡Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Received for publication April 7, 2015; accepted October 27, 2015.

Address correspondence to: Takao Ohtsuka, MD, PhD, Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan (e-mail:

This study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI grant 25670582.

The authors declare no conflicts of interest.

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