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

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

doi:10.1002/cjp2.339

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Title:: High expression of insulinoma-associated protein 1 (INSM1) distinguishes colorectal mixed and pure neuroendocrine carcinomas from conventional adenocarcinomas with diffuse expression of synaptophysin.
Document type:: Journal Article
Author(s):: 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
Abstract:: 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.
Journal title abbreviation:: J Pathol Clin Res
Year:: 2023
Journal volume:: 9
Journal issue:: 6
Pages contribution:: 498-509
Fulltext / DOI:: doi:10.1002/cjp2.339
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/37608427
TUM Institution:: Institut für Allgemeine Pathologie und Pathologische Anatomie (Dr. Mogler komm.)
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