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Different Characteristics in Hormonal Expression Between Primary Pancreatic Neuroendocrine Tumors (pNETs) and Metastatic Sites
Hideyo Kimura*1, Takao Ohtsuka1, Takaaki Fujimoto1, Kenjiro Date1, Taketo Matsunaga1, Yusuke Watanabe1, Koji Tamura1, Atsushi Abe2, Yusuke Mizuuchi2, Yoshihiro Miyasaka1, Daisuke Yamada1, Hisato Igarashi4, Tetsuhide Ito3, Shunichi Takahata1, Yoshinao ODA2, Kazuhiro Mizumoto1, Masao Tanaka1
1Department of Surgery and Oncology Graduate School of Medical Sciences Kyushu University, Fukuoka-city, Japan; 2Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; 3Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; 4Clinical Education Center, Kyushu University Hospital, Fukuoka, Japan
Background: PNETs are known to have heterogeneity in terms of the ability to produce multiple hormones, and we have sometimes experienced different hormonal expression patterns between the primary tumors and metastatic lesions. The aim of this study was to evaluate the heterogeneity of PNETs from the viewpoint of hormonal expressions.
Method: Among 105 patients who underwent pancreatectomy for PNETs at our institution between 1987 and 2014, 20 patients with metastatic PNETs (6 gastrinomas, one insulinoma, one glucagonoma, and 12 non-functioning PNETs (NF-PNETs)) were evaluated. Expressions of representative 4 hormones such as gastrin, insulin, glucagon, and somatostatin were analyzed in both primary and metastatic lesions including lymph nodes in all of 20 patients and hepatic metastasis in 7 patients (2 gastrinomas, and 5 NF-PNETs) by immunohistochemical staining. Immunohistochemical results were considered as positive when the final score (FS) (= the intensity score (IS: 0-3) × the proportional score (PS: 0-4)) was 4 to 12.
Results: The concordance rate (CR) of the hormonal expression pattern between primary tumors and metastatic lesions was 50%. Gastrin was positive in 8 of 20 patients, insulin in 3, glucagon in 3, and somatostatin in 10. Positive expression of 2 or more hormones was found in 6 patients, and that of one or more hormones was found even in 9 of 12 patients whose primary tumors were diagnosed as NF-PNETs. All 8 patients with gastrin-positive primary tumors had gastrin-positive metastatic lymph node (CR 100%), while concordant hormone expression was present in one of 3 with insulin-positive primary tumors (CR 33%), one of 3 with glucagon (CR 33%), and 2of 10 with somatostatin (CR 20%). Two patients had somatostatin-positive metastatic lymph node in spite of negative somatostatin expression in primary tumor. All 7 patients with hepatic metastasis had some hormonal expression in primary tumors; gastrin in 4 patients, insulin in one, glucagon in one, and somatostatin in 3. On the other hand, positive gastrin expression was found in hepatic metastasis in only 2 of 7 patients, one of whom had a gastrin-negative primary tumor, and any hormonal expression was negative in hepatic metastasis in the remaining 5 patients.
Conclusion: It should be recognized that hormonal expressions are often different between primary and metastatic lesions of PNETs.
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