PMID- 38309431
OWN - NLM
STAT- MEDLINE
DCOM- 20240422
LR  - 20240422
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 37
IP  - 4
DP  - 2024 Apr
TI  - PITX2 as a Sensitive and Specific Marker of Midgut Neuroendocrine Tumors: Results 
      from a Cohort of 1157 Primary Neuroendocrine Neoplasms.
PG  - 100442
LID - S0893-3952(24)00022-X [pii]
LID - 10.1016/j.modpat.2024.100442 [doi]
AB  - As neuroendocrine tumors (NETs) often present as metastatic lesions, 
      immunohistochemical assignment to a site of origin is one of the most important 
      tasks in their pathologic assessment. Because a fraction of NETs eludes the 
      typical expression profiles of their primary localization, additional sensitive 
      and specific markers are required to improve diagnostic certainty. We 
      investigated the expression of the transcription factor Pituitary Homeobox 2 
      (PITX2) in a large-scale cohort of 909 NET and 248 neuroendocrine carcinomas 
      (NEC) according to the immunoreactive score (IRS) and correlated PITX2 expression 
      groups with general tumor groups and primary localization. PITX2 expression (all 
      expression groups) was highly sensitive (98.1%) for midgut-derived NET, but not 
      perfectly specific, as non-midgut NET (especially pulmonary/duodenal) were quite 
      frequently weak or moderately positive. The specificity rose to 99.5% for a 
      midgut origin of NET if only a strong PITX2 expression was considered, which was 
      found in only 0.5% (one pancreatic/one pulmonary) of non-midgut NET. In 
      metastases of midgut-derived NET, PITX2 was expressed in all cases (87.5% strong, 
      12.5% moderate), whereas CDX2 was negative or only weakly expressed in 31.3% of 
      the metastases. In NEC, a fraction of cases (14%) showed a weak or moderate PITX2 
      expression, which was not associated with a specific tumor localization. Our 
      study independently validates PITX2 as a very sensitive and specific 
      immunohistochemical marker of midgut-derived NET in a very large collective of 
      neuroendocrine neoplasms. Therefore, our data argue toward implementation into 
      diagnostic panels applied for NET as a firstline midgut marker.
CI  - Copyright (c) 2024 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Grass, Albert
AU  - Grass A
AD  - Department of Pathology, Phillips University Marburg und University Hospital 
      Marburg, Marburg, Germany.
FAU - Kasajima, Atsuko
AU  - Kasajima A
AD  - Department of Pathology, Technical University of Munich, Munich, Germany.
FAU - Foersch, Sebastian
AU  - Foersch S
AD  - Department of Pathology, University Hospital Mainz, Mainz, Germany.
FAU - Kriegsmann, Mark
AU  - Kriegsmann M
AD  - Department of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
FAU - Brobeil, Alexander
AU  - Brobeil A
AD  - Department of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
FAU - Schmitt, Maxime
AU  - Schmitt M
AD  - Department of Pathology, Phillips University Marburg und University Hospital 
      Marburg, Marburg, Germany.
FAU - Wagner, Daniel
AU  - Wagner D
AD  - Department of Pathology, University Hospital Mainz, Mainz, Germany.
FAU - Poppinga, Jelte
AU  - Poppinga J
AD  - Department of Surgery, Phillips University Marburg and University Hospital 
      Marburg, Marburg, Germany.
FAU - Wiese, Dominik
AU  - Wiese D
AD  - Department of Surgery, Phillips University Marburg and University Hospital 
      Marburg, Marburg, Germany.
FAU - Maurer, Elisabeth
AU  - Maurer E
AD  - Department of Surgery, Phillips University Marburg and University Hospital 
      Marburg, Marburg, Germany.
FAU - Kirschbaum, Andreas
AU  - Kirschbaum A
AD  - Department of Surgery, Phillips University Marburg and University Hospital 
      Marburg, Marburg, Germany.
FAU - Muley, Thomas
AU  - Muley T
AD  - Translational Lung Research Center Heidelberg (TLRC-H), Heidelberg, Germany; 
      Translational Research Unit, Thoraxklinik at Heidelberg University Hospital, 
      Heidelberg, Germany.
FAU - Winter, Hauke
AU  - Winter H
AD  - Translational Lung Research Center Heidelberg (TLRC-H), Heidelberg, Germany; 
      Translational Research Unit, Thoraxklinik at Heidelberg University Hospital, 
      Heidelberg, Germany; Department of Thoracic Surgery, Thoraxklinik at Heidelberg 
      University Hospital, Heidelberg, Germany.
FAU - Rinke, Anja
AU  - Rinke A
AD  - Department of Gastroenterology, Endocrinology and Infectious Diseases, Phillips 
      University Marburg and University Hospital Marburg, Marburg, Germany.
FAU - Gress, Thomas M
AU  - Gress TM
AD  - Department of Gastroenterology, Endocrinology and Infectious Diseases, Phillips 
      University Marburg and University Hospital Marburg, Marburg, Germany.
FAU - Kremer, Markus
AU  - Kremer M
AD  - Institute of Pathology, Stadtisches Klinikum Munchen, Munich, Germany.
FAU - Evert, Matthias
AU  - Evert M
AD  - Department of Pathology, University Hospital Regensburg, Regensburg, Germany.
FAU - Markl, Bruno
AU  - Markl B
AD  - Institute of Pathology, University Hospital Augsburg, Augsburg, Germany.
FAU - Quaas, Alexander
AU  - Quaas A
AD  - Institute of Pathology, University Hospital Cologne, Cologne, Germany.
FAU - Eckstein, Markus
AU  - Eckstein M
AD  - Department of Pathology, University Hospital Erlangen, Friedrich-Alexander 
      Universitat Erlangen-Nurnberg, Erlangen, Germany.
FAU - Tschurtschenthaler, Markus
AU  - Tschurtschenthaler M
AD  - Institute for Translational Cancer Research, German Cancer Consortium (DKTK), 
      Partner Site Munich, Munich, Germany.
FAU - Kloppel, Gunter
AU  - Kloppel G
AD  - Department of Pathology, Technical University of Munich, Munich, Germany.
FAU - Denkert, Carsten
AU  - Denkert C
AD  - Department of Pathology, Phillips University Marburg und University Hospital 
      Marburg, Marburg, Germany.
FAU - Bartsch, Detlef K
AU  - Bartsch DK
AD  - Department of Surgery, Phillips University Marburg and University Hospital 
      Marburg, Marburg, Germany.
FAU - Jesinghaus, Moritz
AU  - Jesinghaus M
AD  - Department of Pathology, Phillips University Marburg und University Hospital 
      Marburg, Marburg, Germany. Electronic address: moritz.jesinghaus@uni-marburg.de.
LA  - eng
PT  - Journal Article
DEP - 20240201
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Transcription Factors)
RN  - Gastro-enteropancreatic neuroendocrine tumor
SB  - IM
MH  - Humans
MH  - *Neuroendocrine Tumors/pathology
MH  - Biomarkers, Tumor/metabolism
MH  - *Carcinoma, Neuroendocrine/pathology
MH  - Transcription Factors
MH  - *Pancreatic Neoplasms/pathology
MH  - *Intestinal Neoplasms
MH  - *Stomach Neoplasms
OTO - NOTNLM
OT  - Pituitary Homeobox 2
OT  - midgut
OT  - neuroendocrine carcinoma
OT  - neuroendocrine neoplasms
OT  - neuroendocrine tumor
EDAT- 2024/02/04 00:42
MHDA- 2024/04/22 06:44
CRDT- 2024/02/03 19:29
PHST- 2023/12/10 00:00 [received]
PHST- 2024/01/12 00:00 [revised]
PHST- 2024/01/25 00:00 [accepted]
PHST- 2024/04/22 06:44 [medline]
PHST- 2024/02/04 00:42 [pubmed]
PHST- 2024/02/03 19:29 [entrez]
AID - S0893-3952(24)00022-X [pii]
AID - 10.1016/j.modpat.2024.100442 [doi]
PST - ppublish
SO  - Mod Pathol. 2024 Apr;37(4):100442. doi: 10.1016/j.modpat.2024.100442. Epub 2024 
      Feb 1.