ArticleThe journal of pathology. Clinical research2023
High expression of insulinoma-associated protein 1 (INSM1) distinguishes colorectal mixed and pure neuroendocrine carcinomas from conventional adenocarcinomas with diffuse expression of synaptophysin.
Article in The journal of pathology. Clinical research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 11 citations in OpenAlex.
- What are the Unmet Needs in Managing Digestive Neuroendocrine Carcinomas?Current oncology reports · 2026Review
- Gastrointestinal conventional carcinoma with neuroendocrine differentiation: From pathological phenomenon to clinical importance (Review).Oncology letters · 2026Review
- mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Differentiating well-differentiated neuroendocrine tumors grade 3 from poorly differentiated neuroendocrine carcinomas and adenocarcinoma with neuroendocrine differentiation: a comprehensive review.Virchows Archiv : an international journal of pathology · 2026Review
- MiNEN, amphicrine carcinomas, and conventional carcinomas with neuroendocrine differentiation: diagnostic criteria, open questions, and future perspectives.Virchows Archiv : an international journal of pathology · 2026Review
- Stroma areactive invasion front areas (SARIFA) in 1,298 pT3/pT4 colorectal cancers: A strong prognostic parameter complementing established morphological criteria.Histopathology · 2025Article
- Exploring Intratumoral Heterogeneity in Mixed Neuroendocrine-Nonneuroendocrine Neoplasms with Spatial Transcriptomics: Even More Diverse Than Anticipated.Endocrine pathology · 2025Article
- Prognostic value of clinical parameters and exosomal lncRNA NEAT1_1 in MEN1-related non-functioning pancreatic neuroendocrine tumors.Journal of neuroendocrinology · 2025Article
- Mixed neuroendocrine-non-neuroendocrine neoplasm of the colon treated with laparoscopic resection and adjuvant chemotherapy: a case report.Clinical journal of gastroenterology · 2025Article
- Practical hints for the diagnosis of mixed neuroendocrine-non-neuroendocrine neoplasms of the digestive system.World journal of gastrointestinal oncology · 2024Article
- [Neuroendocrine carcinomas of the gastrointestinal tract : Morphology, molecular pathology, cellular origin].Pathologie (Heidelberg, Germany) · 2024Review
- [Practical application of immunohistochemistry in pancreatic neuroendocrine neoplasms : Tips and pitfalls].Pathologie (Heidelberg, Germany) · 2024Review
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17 authors at 4 institutions in 2 countries.
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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.
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