PMID- 37867522
OWN - NLM
STAT- MEDLINE
DCOM- 20231206
LR  - 20231206
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 14
DP  - 2023
TI  - Multiple endocrine neoplasia type 1 with Zollinger-Ellison syndrome: 
      clinicopathological analysis of a Japanese family with focus on menin 
      immunohistochemistry.
PG  - 1221514
LID - 10.3389/fendo.2023.1221514 [doi]
LID - 1221514
AB  - BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant 
      disorder characterized by the occurrence of multiple epithelial neuroendocrine 
      tumors (NETs) and non-NETs in various organs. MEN1 encodes a 610-amino acid-long 
      tumor suppressor protein, menin. The optimal treatment for multiple tumors, 
      identification of the most critical tumors for patient prognosis, and menin 
      immunohistochemistry findings remain controversial. Therefore, we aimed to 
      elucidate these issues through a histological analysis of tumors and tumor-like 
      lesions in a Japanese family, comprising a father and his two sons, who had MEN1 
      with Zollinger-Ellison syndrome (ZES). PATIENTS AND METHODS: All family members 
      had a germline alteration in exon 10, c.1714-1715 del TC of MEN1, and exhibited 
      multiple synchronous and metachronous tumors. The patients had pulmonary NETs, 
      hyperparathyroidism, hypergastrinemia, pituitary adenomas, pancreaticoduodenal 
      NETs, adrenocortical adenoma with myelolipoma, nodular goiter of the thyroid, 
      lipomas, and angiofibroma. Most tumors were resected and histologically examined. 
      We compared their clinical courses and tumor histology, and conducted menin 
      immunohistochemistry (IHC). RESULTS: Two patients died of pulmonary NET G2. One 
      patient who underwent pancreaticoduodenectomy was cured of ZES; however, the two 
      other patients who did not undergo pancreaticoduodenectomy suffered persistent 
      ZES despite treatment with octreotide. Menin IHC revealed varying NET 
      intensities, ranging from positive to negative stains. CONCLUSION: 
      Pancreaticoduodenectomy is the most effective treatment for ZES. Long-term 
      follow-up is essential for pulmonary NET G2 owing to the risk of distant 
      metastasis and/or multiplicity. Moreover, the variability of menin IHC in 
      MEN1-related tumors may indicate the pattern of tumor formation rather than the 
      diagnostic utility of menin in MEN1.
CI  - Copyright (c) 2023 Kimura, Hirata, Iwashiro, Kijima, Takayasu, Yamagata, Sakihara, 
      Uchino and Ohara.
FAU - Kimura, Noriko
AU  - Kimura N
AD  - Department of Clinical Research, National Hospital Organization Hakodate 
      Hospital, Hakodate, Hokkaido, Japan.
AD  - Department of Diagnostic Pathology, National Hospital Organization Hakodate 
      Hospital, Hakodate, Hokkaido, Japan.
FAU - Hirata, Yasuji
AU  - Hirata Y
AD  - Department of Hematology and Oncology, National Hospital Organization Hakodate 
      Hospital, Hakodate, Hokkaido, Japan.
FAU - Iwashiro, Nozomu
AU  - Iwashiro N
AD  - Department of Surgery, National Hospital Organization Hakodate Hospital, 
      Hakodate, Hokkaido, Japan.
FAU - Kijima, Hiroshi
AU  - Kijima H
AD  - Department of Pathology, Hirosaki University Graduate School of Medicine, 
      Hirosaki, Aomori, Japan.
FAU - Takayasu, Shinobu
AU  - Takayasu S
AD  - Department of Endocrinology and Metabolism, Hirosaki University Graduate School 
      of Medicine and Hospital, Hirosaki, Aomori, Japan.
FAU - Yamagata, Satoshi
AU  - Yamagata S
AD  - Department of Endocrinology and Metabolism, Hirosaki University Graduate School 
      of Medicine and Hospital, Hirosaki, Aomori, Japan.
AD  - Institute of Human Nutrition, Columbia University Irving Medical Center, New 
      York, NY, United States.
FAU - Sakihara, Satoru
AU  - Sakihara S
AD  - Department of Endocrinology and Metabolism, Hirosaki University Graduate School 
      of Medicine and Hospital, Hirosaki, Aomori, Japan.
AD  - Division of Diabetes and Endocrinology, Aomori Rosai Hospital, Aomori, Japan.
FAU - Uchino, Shinya
AU  - Uchino S
AD  - Department of Endocrine Surgery, Noguchi Thyroid Clinic and Hospital Foundation, 
      Beppu, Oita, Japan.
FAU - Ohara, Masanori
AU  - Ohara M
AD  - Department of Surgery, National Hospital Organization Hakodate Hospital, 
      Hakodate, Hokkaido, Japan.
LA  - eng
PT  - Journal Article
DEP - 20231006
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
RN  - 0 (Transcription Factors)
RN  - 0 (MEN1 protein, human)
SB  - IM
MH  - Humans
MH  - East Asian People
MH  - Immunohistochemistry
MH  - *Multiple Endocrine Neoplasia Type 1/genetics/surgery/diagnosis
MH  - *Neuroendocrine Tumors
MH  - Transcription Factors
MH  - *Zollinger-Ellison Syndrome/diagnosis/genetics/pathology
PMC - PMC10588651
OTO - NOTNLM
OT  - Zollinger-Ellison syndrome
OT  - immunohistochemistry
OT  - menin
OT  - metastasis
OT  - multiple endocrine neoplasia type 1
OT  - neuroendocrine tumor
OT  - prognosis
OT  - pulmonary atypical carcinoid
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/10/23 06:47
MHDA- 2023/11/01 12:43
PMCR- 2023/01/01
CRDT- 2023/10/23 04:25
PHST- 2023/05/12 00:00 [received]
PHST- 2023/09/18 00:00 [accepted]
PHST- 2023/11/01 12:43 [medline]
PHST- 2023/10/23 06:47 [pubmed]
PHST- 2023/10/23 04:25 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2023.1221514 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2023 Oct 6;14:1221514. doi: 
      10.3389/fendo.2023.1221514. eCollection 2023.