PMID- 37951531 OWN - NLM STAT- MEDLINE DCOM- 20240117 LR - 20240117 IS - 1872-8057 (Electronic) IS - 0303-7207 (Linking) VI - 581 DP - 2024 Feb 1 TI - Comparison of INSM1 immunostaining with established neuroendocrine markers synaptophysin and chromogranin A in over 14,000 neuroendocrine and non-neuroendocrine tumors. PG - 112106 LID - S0303-7207(23)00257-5 [pii] LID - 10.1016/j.mce.2023.112106 [doi] AB - INSM1 is a transcription factor protein which is increasingly used as an immunohistochemical marker for neuroendocrine differentiation. To determine the prevalence of INSM1 expression in tumors and its expression pattern in normal tissues, tissue microarrays containing 14,908 samples from 117 different tumor types/subtypes as well as 76 different normal tissues were analyzed by immunohistochemistry. INSM1 was positive in 89.2% of 471 neuroendocrine neoplasms (NEN) and in 3.5% of 11,815 non-neuroendocrine neoplasms that were successfully analyzed. At least an occasional weak INSM1 positivity was observed in 59 different non-neuroendocrine tumor entities, of which 15 entities contained at least one case with strong INSM1 staining. A comparison with synaptophysin and chromogranin A staining revealed that in NEN, synaptophysin showed the highest sensitivity (93.3%), followed by INSM1 (89.2%) and chromogranin A (87.5%). In neuroendocrine carcinomas (NEC), sensitivity was highest for INSM1 (88.0%), followed by synaptophysin (86.5%) and chromogranin A (66.4%). If INSM1 was used as an additional marker, the sensitivity for detecting neuroendocrine differentiation in NEN increased from 96.6% (synaptophysin and chromogranin A) to 97.2% (synaptophysin, chromogranin A and INSM1). Our study shows that INSM1 is a useful additional marker for neuroendocrine differentiation with high sensitivity, particularly in NEC. CI - Copyright (c) 2023 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Moller, Katharina AU - Moller K AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Uhlig, Ria AU - Uhlig R AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Gorbokon, Natalia AU - Gorbokon N AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Dum, David AU - Dum D AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Menz, Anne AU - Menz A AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Buscheck, Franziska AU - Buscheck F AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Luebke, Andreas M AU - Luebke AM AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Hube-Magg, Claudia AU - Hube-Magg C AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Hinsch, Andrea AU - Hinsch A AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Hoflmayer, Doris AU - Hoflmayer D AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Fraune, Christoph AU - Fraune C AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Lebok, Patrick AU - Lebok P AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany. FAU - Weidemann, Soren AU - Weidemann S AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Lennartz, Maximilian AU - Lennartz M AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Jacobsen, Frank AU - Jacobsen F AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Clauditz, Till S AU - Clauditz TS AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Steurer, Stefan AU - Steurer S AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Burandt, Eike AU - Burandt E AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Krech, Rainer AU - Krech R AD - Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany. FAU - Krech, Till AU - Krech T AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany. FAU - Marx, Andreas H AU - Marx AH AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Pathology, Academic Hospital Fuerth, Fuerth Germany. FAU - Sauter, Guido AU - Sauter G AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Simon, Ronald AU - Simon R AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: r.simon@uke.de. FAU - Bernreuther, Christian AU - Bernreuther C AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Minner, Sarah AU - Minner S AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. LA - eng PT - Comparative Study PT - Journal Article DEP - 20231110 PL - Ireland TA - Mol Cell Endocrinol JT - Molecular and cellular endocrinology JID - 7500844 RN - 0 (Biomarkers, Tumor) RN - 0 (Chromogranin A) RN - 147955-03-1 (INSM1 protein, human) RN - 0 (Repressor Proteins) RN - 0 (Synaptophysin) SB - IM MH - Humans MH - Biomarkers, Tumor/metabolism MH - *Carcinoma, Neuroendocrine/pathology MH - Chromogranin A/metabolism MH - *Neuroendocrine Tumors/pathology MH - Repressor Proteins/metabolism MH - Sensitivity and Specificity MH - Synaptophysin/metabolism OTO - NOTNLM OT - INSM1 OT - Immunohistochemistry OT - Insulin-associated antigen-1 (IA-1) OT - TMA OT - Tissue microarray COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The INSM1 antibody (clone MSVA-456R) was provided from MS Validated Antibodies GmbH (owned by a family member of GS). EDAT- 2023/11/12 00:42 MHDA- 2024/01/15 12:42 CRDT- 2023/11/11 19:18 PHST- 2023/06/12 00:00 [received] PHST- 2023/10/04 00:00 [revised] PHST- 2023/11/03 00:00 [accepted] PHST- 2024/01/15 12:42 [medline] PHST- 2023/11/12 00:42 [pubmed] PHST- 2023/11/11 19:18 [entrez] AID - S0303-7207(23)00257-5 [pii] AID - 10.1016/j.mce.2023.112106 [doi] PST - ppublish SO - Mol Cell Endocrinol. 2024 Feb 1;581:112106. doi: 10.1016/j.mce.2023.112106. Epub 2023 Nov 10.