PMID- 36029394
OWN - NLM
STAT- MEDLINE
DCOM- 20221202
LR  - 20221202
IS  - 1559-0097 (Electronic)
IS  - 1046-3976 (Linking)
VI  - 33
IP  - 4
DP  - 2022 Dec
TI  - PHOX2B is a Sensitive and Specific Marker for the Histopathological Diagnosis of 
      Pheochromocytoma and Paraganglioma.
PG  - 506-518
LID - 10.1007/s12022-022-09730-4 [doi]
AB  - Pheochromocytomas (PCCs) and paragangliomas (PGLs) are non-epithelial 
      neuroendocrine neoplasms originating from the adrenal medulla and paraganglion of 
      the sympathetic and parasympathetic nervous system, respectively. PCCs and PGLs 
      show histological similarities with other epithelial neuroendocrine neoplasms and 
      olfactory neuroblastomas (ONBs), and the differential diagnosis of PGLs is 
      particularly difficult. Therefore, we compared the sensitivity of PHOX2A, PHOX2B, 
      and tyrosine hydroxylase (TH) in the histopathological diagnosis of PCCs and PGLs 
      immunohistochemically using the tissue microarrays of 297 neoplasms including 
      PCCs, PGLs, neuroblastomas, ganglioneuromas, epithelial neuroendocrine neoplasms, 
      and ONBs. Using cutoff values of 25%, 5%, and 5% of tumor cells expressing 
      PHOX2A, PHOX2B, and TH, respectively, as positive, 40 of 51 PCCs, 32 of 33 
      parasympathetic/head and neck PGLs (HNPGLs), 17 of 19 
      sympathetic/thoracoabdominal PGLs (TAPGLs), and 12 of 152 epithelial 
      neuroendocrine neoplasms, including 123 well-differentiated and 29 poorly 
      differentiated neuroendocrine neoplasms, were PHOX2A-positive. All 51 PCCs, 33 
      HNPGLs, and 19 TAPGLs were PHOX2B-positive, while all 152 epithelial 
      neuroendocrine neoplasms were PHOX2B-negative. Moreover, 50 of 51 PCCs, 13 of 33 
      HNPGLs, all TAPGLs, and 12 of 152 epithelial neuroendocrine neoplasms were 
      TH-positive. All ONBs were negative for PHOX2A, PHOX2B, and TH. PHOX2B was the 
      most sensitive and specific diagnostic marker for PCCs and PGLs among PHOX2A, 
      PHOX2B, and TH. PHOX2B can facilitate identification of PCCs and PGLs from 
      epithelial neuroendocrine neoplasms and ONBs, especially in the case of HNPGLs, 
      in which TH is often negative.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Miyauchi, Minami
AU  - Miyauchi M
AD  - Department of Human Pathology, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Akashi, Takumi
AU  - Akashi T
AD  - Department of Diagnostic Pathology, Graduate School of Medical and Dental 
      Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 
      113-8519, Japan. akashi.path@tmd.ac.jp.
AD  - Division of Surgical Pathology, Tokyo Medical and Dental University Hospital, 
      Tokyo, Japan. akashi.path@tmd.ac.jp.
FAU - Furukawa, Asuka
AU  - Furukawa A
AD  - Department of Human Pathology, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Uchida, Keisuke
AU  - Uchida K
AD  - Department of Human Pathology, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University, Tokyo, Japan.
AD  - Division of Surgical Pathology, Tokyo Medical and Dental University Hospital, 
      Tokyo, Japan.
FAU - Tamura, Tomoki
AU  - Tamura T
AD  - Division of Surgical Pathology, Tokyo Medical and Dental University Hospital, 
      Tokyo, Japan.
FAU - Ando, Noboru
AU  - Ando N
AD  - Division of Surgical Pathology, Tokyo Medical and Dental University Hospital, 
      Tokyo, Japan.
FAU - Kirimura, Susumu
AU  - Kirimura S
AD  - Division of Surgical Pathology, Tokyo Medical and Dental University Hospital, 
      Tokyo, Japan.
FAU - Shintaku, Hiroshi
AU  - Shintaku H
AD  - Division of Surgical Pathology, Tokyo Medical and Dental University Hospital, 
      Tokyo, Japan.
FAU - Yamamoto, Kurara
AU  - Yamamoto K
AD  - Department of Human Pathology, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Ito, Takashi
AU  - Ito T
AD  - Department of Human Pathology, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Miura, Keiko
AU  - Miura K
AD  - Division of Surgical Pathology, Tokyo Medical and Dental University Hospital, 
      Tokyo, Japan.
FAU - Kayamori, Kou
AU  - Kayamori K
AD  - Department of Oral Pathology, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Ariizumi, Yosuke
AU  - Ariizumi Y
AD  - Department of Head and Neck Surgery, Graduate School of Medical and Dental 
      Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Asakage, Takahiro
AU  - Asakage T
AD  - Department of Head and Neck Surgery, Graduate School of Medical and Dental 
      Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Kudo, Atsushi
AU  - Kudo A
AD  - Department of Hepatobiliary and Pancreatic Surgery, Tokyo Medical and Dental 
      University Hospital, Tokyo, Japan.
FAU - Tanabe, Minoru
AU  - Tanabe M
AD  - Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medical 
      and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Fujii, Yasuhisa
AU  - Fujii Y
AD  - Department of Thoracic Surgery, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Ishibashi, Hironori
AU  - Ishibashi H
AD  - Department of Urology, Graduate School of Medical and Dental Sciences, Tokyo 
      Medical and Dental University, Tokyo, Japan.
FAU - Okubo, Kenichi
AU  - Okubo K
AD  - Department of Urology, Graduate School of Medical and Dental Sciences, Tokyo 
      Medical and Dental University, Tokyo, Japan.
FAU - Murakami, Masanori
AU  - Murakami M
AD  - Department of Molecular Endocrinology and Metabolism, Graduate School of Medical 
      and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Yamada, Tetsuya
AU  - Yamada T
AD  - Department of Molecular Endocrinology and Metabolism, Graduate School of Medical 
      and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Takemoto, Akira
AU  - Takemoto A
AD  - Division of Surgical Pathology, Tokyo Medical and Dental University Hospital, 
      Tokyo, Japan.
AD  - Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Bae, Yuan
AU  - Bae Y
AD  - Department of Pathology, Japanese Red Cross Medical Center, Tokyo, Japan.
FAU - Eishi, Yoshinobu
AU  - Eishi Y
AD  - Department of Human Pathology, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Ohashi, Kenichi
AU  - Ohashi K
AD  - Department of Human Pathology, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University, Tokyo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20220827
PL  - United States
TA  - Endocr Pathol
JT  - Endocrine pathology
JID - 9009288
RN  - 0 (Transcription Factors)
RN  - 0 (Biomarkers)
SB  - IM
MH  - Humans
MH  - *Pheochromocytoma/diagnosis/pathology
MH  - *Paraganglioma/diagnosis/pathology
MH  - *Adrenal Gland Neoplasms/diagnosis/pathology
MH  - *Paraganglioma, Extra-Adrenal
MH  - Transcription Factors
MH  - Biomarkers
OTO - NOTNLM
OT  - Immunohistochemistry
OT  - PHOX2A
OT  - PHOX2B
OT  - Paraganglioma
OT  - Pheochromocytoma
OT  - Tyrosine hydroxylase
EDAT- 2022/08/28 06:00
MHDA- 2022/12/03 06:00
CRDT- 2022/08/27 11:17
PHST- 2022/08/19 00:00 [accepted]
PHST- 2022/08/28 06:00 [pubmed]
PHST- 2022/12/03 06:00 [medline]
PHST- 2022/08/27 11:17 [entrez]
AID - 10.1007/s12022-022-09730-4 [pii]
AID - 10.1007/s12022-022-09730-4 [doi]
PST - ppublish
SO  - Endocr Pathol. 2022 Dec;33(4):506-518. doi: 10.1007/s12022-022-09730-4. Epub 2022 
      Aug 27.