Attenuated expression of menin and p27 Kip1 in an aggressive case of multiple endocrine neoplasia type 1 (MEN1) associated with an atypical prolactinoma and a malignant pancreatic endocrine tumor
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- Ishida Emi
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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- Yamada Masanobu
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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- Horiguchi Kazuhiko
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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- Taguchi Ryo
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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- Ozawa Atsushi
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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- Shibusawa Nobuyuki
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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- Hashimoto Koshi
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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- Satoh Tetsuro
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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- Yoshida Sachiko
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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- Tanaka Yoshiki
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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- Yokota Machiko
- Department of Pathology, Gunma University Graduate School of Medicine, Maebashi, Japan
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- Tosaka Masahiko
- Department of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Japan
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- Hirato Junko
- Department of Pathology, Gunma University Graduate School of Medicine, Maebashi, Japan
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- Yamada Shozo
- Department of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Tokyo, Japan
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- Yoshimoto Yuhei
- Department of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Japan
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- Mori Masatomo
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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抄録
Tumors in multiple endocrine neoplasia type 1 (MEN1) are generally benign. Since information on the pathogenesis of MEN1 in malignant cases is limited, we conducted genetic analysis and compared the expression of menin, p27Kip1(p27)/CDKN1B and p18Ink4C(p18)/CDKN2C with levels in benign cases. We describe the case of a 56 year-old male with an atypical prolactinoma and malignant pancreatic neuroenocrine tumor. At age 50, he had undergone transsphenoidal surgery to remove a prolactinoma. However, the tumor relapsed twice. Histological analysis of the recurrent prolactinoma revealed the presence of prolactin, a high MIB-1 index (32.1 %), p53-positive cells (0.2%), and an unusual association with FSH-positive cells. A few years later, he was also found to have a non-functioning pancreatic tumor with probable metastasis to the extradullar region. The metastatic region tested positive for chromogranin and CD56, and negative for prolactin, with 1.2 % of cells p53-positive. Although genetic analyses of the MEN1, p27, and p18 genes demonstrated no mutation, numbers of menin, p27 and p18 immuno-positive cells were significantly down-regulated in the recurrent prolactinoma, but that of p18 was intact in the metastatic region. Furthermore, MEN1 and p27 mRNA levels of the recurrent prolactinoma were down-regulated, particularly the MEN1 mRNA level, compared to levels in 10 cases of benign prolactinoma, while the p18 mRNA level was similar to that of normal pituitary. The tumor in this case may be a subtype of MEN1 showing more aggressive and malignant features probably induced by low levels of menin and p27.
収録刊行物
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- Endocrine Journal
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Endocrine Journal 58 (4), 287-296, 2011
一般社団法人 日本内分泌学会
