PMID- 38416360
OWN - NLM
STAT- MEDLINE
DCOM- 20240318
LR  - 20240318
IS  - 1559-0097 (Electronic)
IS  - 1046-3976 (Linking)
VI  - 35
IP  - 1
DP  - 2024 Mar
TI  - Hand2 Immunohistochemistry in the Diagnosis of Paragangliomas and Other 
      Neuroendocrine Neoplasms.
PG  - 14-24
LID - 10.1007/s12022-024-09803-6 [doi]
AB  - Hand2 is a core transcription factor responsible for chromaffin cell 
      differentiation. However, its potential utility in surgical pathology has not 
      been studied. Thus, we aimed to investigate its expression in paragangliomas, 
      other neuroendocrine neoplasms (NENs), and additional non-neuroendocrine tumors. 
      We calibrated Hand2 immunohistochemistry on adrenal medulla cells and analyzed 
      H-scores in 46 paragangliomas (PGs), 9 metastatic PGs, 21 cauda equina 
      neuroendocrine tumors (CENETs), 48 neuroendocrine carcinomas (NECs), 8 olfactory 
      neuroblastomas (ONBs), 110 well-differentiated NETs (WDNETs), 10 adrenal cortical 
      carcinomas, 29 adrenal cortical adenomas, 8 melanomas, 41 different carcinomas, 
      and 10 gastrointestinal stromal tumors (GISTs). Both tissue microarrays (TMAs) 
      and whole sections (WSs) were studied. In 171 NENs, previously published data on 
      Phox2B and GATA3 were correlated with Hand2. Hand2 was positive in 98.1% (54/55) 
      PGs, but only rarely in WDNETs (9.6%, 10/104), CENETs (9.5%, 2/21), NECs (4.2%, 
      2/48), or ONBs (12.5%, 1/8). Any Hand2 positivity was 98.1% sensitive and 91.7% 
      specific for the diagnosis of PG. The Hand2 H-score was significantly higher in 
      primary PGs compared to Hand2-positive WDNETs (median 166.3 vs. 7.5; p < 0.0001). 
      Metastatic PGs were positive in 88.9% (8/9). No Hand2 positivity was observed in 
      any adrenal cortical neoplasm or other non-neuroendocrine tumors, with exception 
      of 8/10 GISTs. Parasympathetic PGs showed a higher Hand2 H-score compared to 
      sympathetic PGs (median H-scores 280 vs. 104, p < 0.0001). Hand2 positivity in 
      NENs serves as a reliable marker of primary and metastatic PG, since other NENs 
      only rarely exhibit limited Hand2 positivity.
CI  - (c) 2024. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Soukup, Jiri
AU  - Soukup J
AUID- ORCID: 0000-0001-7169-4386
AD  - Department of Pathology, Military University Hospital Prague, U Vojenske 
      Nemocnice 1200, Praha 6, 169 02, Prague, Czech Republic. 2jiri.soukup@gmail.com.
AD  - The Fingerland Department of Pathology, Charles University, Faculty of Medicine 
      in Hradec Kralove and University Hospital Hradec Kralove, Sokolska 582, 500 05, 
      Hradec Kralove, Czech Republic. 2jiri.soukup@gmail.com.
AD  - Department of Pathology, Charles University, First Faculty of Medicine and 
      General University Hospital in Prague, Studnickova, 2039, 128 00, Nove Mesto, 
      Prague, Czech Republic. 2jiri.soukup@gmail.com.
FAU - Manethova, Monika
AU  - Manethova M
AD  - The Fingerland Department of Pathology, Charles University, Faculty of Medicine 
      in Hradec Kralove and University Hospital Hradec Kralove, Sokolska 582, 500 05, 
      Hradec Kralove, Czech Republic.
FAU - Stejskal, Vaclav
AU  - Stejskal V
AD  - The Fingerland Department of Pathology, Charles University, Faculty of Medicine 
      in Hradec Kralove and University Hospital Hradec Kralove, Sokolska 582, 500 05, 
      Hradec Kralove, Czech Republic.
FAU - Novakova, Marie
AU  - Novakova M
AD  - Department of Pathology, Military University Hospital Prague, U Vojenske 
      Nemocnice 1200, Praha 6, 169 02, Prague, Czech Republic.
FAU - Duskova, Jaroslava
AU  - Duskova J
AD  - Department of Pathology, Charles University, First Faculty of Medicine and 
      General University Hospital in Prague, Studnickova, 2039, 128 00, Nove Mesto, 
      Prague, Czech Republic.
FAU - Hornychova, Helena
AU  - Hornychova H
AD  - The Fingerland Department of Pathology, Charles University, Faculty of Medicine 
      in Hradec Kralove and University Hospital Hradec Kralove, Sokolska 582, 500 05, 
      Hradec Kralove, Czech Republic.
FAU - Hacova, Maria
AU  - Hacova M
AD  - Department of Pathology, The Regional Hospital Pardubice, Pardubice, Czech 
      Republic.
FAU - Staniczkova-Zambo, Iva
AU  - Staniczkova-Zambo I
AD  - 1st Department of Pathology, St. Anne's University Hospital and Faculty of 
      Medicine , Masaryk University, Pekarska 664/53, 602 00, Brno-stred, Brno, Czech 
      Republic.
FAU - Zelinka, Tomas
AU  - Zelinka T
AD  - Centre for Hypertension, 3rd Department of Medicine, Charles University, First 
      Faculty of Medicine and General University Hospital in Prague, Prague, Czech 
      Republic.
FAU - Kosak, Mikulas
AU  - Kosak M
AD  - Department of Internal Medicine, First Faculty of Medicine, Charles University 
      and Military University Hospital, Prague, Czech Republic.
FAU - Cesak, Tomas
AU  - Cesak T
AD  - Department of Neurosurgery, Charles University, Faculty of Medicine in Hradec 
      Kralove and University Hospital Hradec Kralove, Sokolska 582, 500 05, Hradec 
      Kralove, Czech Republic.
FAU - Netuka, David
AU  - Netuka D
AD  - Department of Neurosurgery and Neurooncology, 1st Medical Faculty, Charles 
      University, Military University Hospital Prague, U Vojenske Nemocnice 1200, Praha 
      6, 169 02, Prague, Czech Republic.
FAU - Ryska, Ales
AU  - Ryska A
AD  - The Fingerland Department of Pathology, Charles University, Faculty of Medicine 
      in Hradec Kralove and University Hospital Hradec Kralove, Sokolska 582, 500 05, 
      Hradec Kralove, Czech Republic.
FAU - Gabalec, Filip
AU  - Gabalec F
AD  - 4th Department of Internal Medicine, Charles University, Faculty of Medicine in 
      Hradec Kralove and University Hospital Hradec Kralove, Sokolska 582, 500 05, 
      Hradec Kralove, Czech Republic.
LA  - eng
GR  - LM2023033/BBMRI-CZ/
GR  - Cooperatio DIAG/Univerzita Karlova v Praze/
GR  - Cooperatio METD/Univerzita Karlova v Praze/
GR  - EF16_013/0001674/European Regional Development Fund-Project BBMRI-CZ/
GR  - conceptual development of research organization 00064165/Ministerstvo 
      Zdravotnictvi Ceske Republiky/
GR  - NU23-01-00323/Ministerstvo Zdravotnictvi Ceske Republiky/
GR  - 22-07091S/Grantova Agentura Ceske Republiky/
GR  - MO 1012/Ministerstvo Obrany Ceske Republiky/
PT  - Journal Article
DEP - 20240228
PL  - United States
TA  - Endocr Pathol
JT  - Endocrine pathology
JID - 9009288
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Humans
MH  - Immunohistochemistry
MH  - *Neuroendocrine Tumors/pathology
MH  - Transcription Factors/metabolism
MH  - *Paraganglioma/diagnosis/pathology
MH  - *Carcinoma, Neuroendocrine/pathology
OTO - NOTNLM
OT  - GATA3
OT  - Hand2
OT  - Neuroendocrine tumors
OT  - Paraganglioma
OT  - Phox2B
OT  - dHand
EDAT- 2024/02/28 12:42
MHDA- 2024/03/18 06:42
CRDT- 2024/02/28 11:14
PHST- 2024/02/08 00:00 [accepted]
PHST- 2024/03/18 06:42 [medline]
PHST- 2024/02/28 12:42 [pubmed]
PHST- 2024/02/28 11:14 [entrez]
AID - 10.1007/s12022-024-09803-6 [pii]
AID - 10.1007/s12022-024-09803-6 [doi]
PST - ppublish
SO  - Endocr Pathol. 2024 Mar;35(1):14-24. doi: 10.1007/s12022-024-09803-6. Epub 2024 
      Feb 28.