title: INSM1: A Novel Immunohistochemical and Molecular Marker for Neuroendocrine and Neuroepithelial Neoplasms.
abstract: OBJECTIVE
  Neuroendocrine neoplasms (NENs) are heterogeneous neoplasms, which are sometimes malignant, although predicting metastasis is difficult. INSM1 is a transcription factor expressed transiently in embryonic neuroendocrine (NE) tissue, thought to coordinate termination of cell division with differentiation of NE and neuroepithelial cells. In adult tissues, INSM1 has been identified in multiple tumors of NE or neuroepithelial origin but has not been thoroughly investigated as a potential neoplastic marker.
  
  
  METHODS
  We evaluated INSM1 as a semiquantitative immunohistochemical (IHC) marker for NE and neuroepithelial neoplasms and as a quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) marker for gastrointestinal NENs (GI-NENs).
  
  
  RESULTS
  Using IHC, we found in normal adult tissue that INSM1 expression was highly restricted to nuclei of NE cells and tissues. INSM1 was not detected in any adult nonneoplastic, non-NE tissue. In neoplastic tissue, INSM1 was detectable by IHC in 88.3% of 129 NEN specimens. In contrast, INSM1 was detected by IHC in only one of 27 neoplasms without a neuroepithelial or NE component. Using qRT-PCR, we evaluated INSM1 gene expression in 113 GI-NEN specimens.
  
  
  CONCLUSIONS
  INSM1 expression was significantly increased in neoplastic vs nonneoplastic tissue. Furthermore, among midgut GI-NENs, neoplasms with known metastases showed significantly higher expression than those that had not yet metastasized.
authors.affiliation: From the Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital and Clinics, Madison. JRosenbaum@path.wustl.edu.
authors.forename: Jason N
authors.initials: JN
authors.lastname: Rosenbaum
authors.affiliation: From the Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital and Clinics, Madison.
authors.forename: Zhenying
authors.initials: Z
authors.lastname: Guo
authors.affiliation: From the Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital and Clinics, Madison.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Baus
authors.affiliation: From the Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital and Clinics, Madison.
authors.forename: Helen
authors.initials: H
authors.lastname: Werner
authors.affiliation: From the Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital and Clinics, Madison.
authors.forename: William M
authors.initials: WM
authors.lastname: Rehrauer
authors.affiliation: From the Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital and Clinics, Madison.
authors.forename: Ricardo V
authors.initials: RV
authors.lastname: Lloyd
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D006801:Humans; D007150:Immunohistochemistry; D018302:Neoplasms, Neuroepithelial / Q000175:diagnosis*; D018358:Neuroendocrine Tumors / Q000175:diagnosis*; D012097:Repressor Proteins / Q000032:analysis / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D012097:Repressor Proteins; C087342:INSM1 protein, human
keywords: Cancer; IHC; INSM1; NEN; Neuroendocrine; Neuroepithelial