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Litmeyer, Anne‐Sophie; Konukiewitz, Björn; Kasajima, Atsuko; Foersch, Sebastian; Schicktanz, Felix; Schmitt, Maxime; Kellers, Franziska; Grass, Albert; Jank, Paul; Lehman, Bettina; Gress, Thomas M; Rinke, Anja; Bartsch, Detlef K; Denkert, Carsten; Weichert, Wilko; Klöppel, Günter; Jesinghaus, Moritz

High expression of insulinoma‐associated protein 1 (INSM1) distinguishes colorectal mixed and pure neuroendocrine carcinomas from conventional adenocarcinomas with diffuse expression of synaptophysin

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  • Medientyp: E-Artikel
  • Titel: High expression of insulinoma‐associated protein 1 (INSM1) distinguishes colorectal mixed and pure neuroendocrine carcinomas from conventional adenocarcinomas with diffuse expression of synaptophysin
  • Beteiligte: Litmeyer, Anne‐Sophie; Konukiewitz, Björn; Kasajima, Atsuko; Foersch, Sebastian; Schicktanz, Felix; Schmitt, Maxime; Kellers, Franziska; Grass, Albert; Jank, Paul; Lehman, Bettina; Gress, Thomas M; Rinke, Anja; Bartsch, Detlef K; Denkert, Carsten; Weichert, Wilko; Klöppel, Günter; Jesinghaus, Moritz
  • Erschienen: Wiley, 2023
  • Erschienen in: The Journal of Pathology: Clinical Research
  • Sprache: Englisch
  • DOI: 10.1002/cjp2.339
  • ISSN: 2056-4538
  • Schlagwörter: Pathology and Forensic Medicine
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Complementary to synaptophysin and chromogranin A, insulinoma‐associated protein 1 (INSM1) has emerged as a sensitive marker for the diagnosis of neuroendocrine neoplasms. Since there are no comparative data regarding INSM1 expression in conventional colorectal adenocarcinomas (CRCs) and colorectal mixed adenoneuroendocrine carcinomas/neuroendocrine carcinomas (MANECs/NECs), we examined INSM1 in a large cohort of conventional CRCs and MANECs/NECs. In conventional CRC, we put a special focus on conventional CRC with diffuse expression of synaptophysin, which carry the risk of being misinterpreted as a MANEC or a NEC. We investigated INSM1 according to the immunoreactive score in our main cohort of 1,033 conventional CRCs and 21 MANECs/NECs in comparison to the expression of synaptophysin and chromogranin A and correlated the results with clinicopathological parameters and patient survival. All MANECs/NECs expressed INSM1, usually showing high or moderate expression (57% high, 34% moderate, and 9% low), which distinguished them from conventional CRCs, which were usually INSM1 negative or low, even if they diffusely expressed synaptophysin. High expression of INSM1 was not observed in conventional CRCs. Chromogranin A was negative/low in most conventional CRCs (99%), but also in most MANECs/NECs (66%). Comparable results were observed in our independent validation cohorts of conventional CRC (<jats:italic>n</jats:italic> = 274) and MANEC/NEC (<jats:italic>n</jats:italic> = 19). Similar to synaptophysin, INSM1 expression had no prognostic relevance in conventional CRCs, while true MANEC/NEC showed a highly impaired survival in univariate and multivariate analyses (e.g. disease‐specific survival: <jats:italic>p</jats:italic> &lt; 0.001). MANECs/NECs are a highly aggressive variant of colorectal cancer, which must be reliably identified. High expression of INSM1 distinguishes MANEC/NEC from conventional CRCs with diffuse expression of the standard neuroendocrine marker synaptophysin, which do not share the same dismal prognosis. Therefore, high INSM1 expression is a highly specific/sensitive marker that is supportive for the diagnosis of true colorectal MANEC/NEC.</jats:p>
  • Zugangsstatus: Freier Zugang