High expression of insulinoma-associated protein 1 (INSM1) distinguishes colorectal mixed and pure neuroendocrinecarcinomas from conventional adenocarcinomas with diffuseexpression of synaptophysin

High expression of insulinoma-associated protein 1 (INSM1) distinguishes colorectal mixed and pure neuroendocrinecarcinomas from conventional adenocarcinomas with diffuseexpression of synaptophysin

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...

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Autoren: 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
Format: Artikel
Sprache:Englisch
Veröffentlicht: Philipps-Universität Marburg 2023
Schlagworte:
neuroendocrine carcinoma
colorectal carcinoma
conventional adenocarcinoma
INSM1
Medizin
synaptophysin
Medical sciences Medicine
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Zusammenfassung: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 (n = 274) and MANEC/NEC (n = 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: p < 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.
Beschreibung:Gefördert durch den Open-Access-Publikationsfonds der UB Marburg.
DOI:10.1002/cjp2.339

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