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Histopathology. 2019 May 11. doi: 10.1111/his.13899. [Epub ahead of print]

INSM1 Expression in Primary and Metastatic Neuroendocrine Neoplasms of the Gastrointestinal and Pancreatobiliary Tracts.

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Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri.
Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri.
Current Institution: Department of Pathology, Yale School of Medicine, New Haven, Connecticut.
Division of Gastroenterology, Washington University School of Medicine, Saint Louis, Missouri.



Insulinoma associated protein 1 (INSM1) is a transcription factor expressed in developing and mature neuroendocrine tissue. Recent studies have demonstrated INSM1 as a sensitive marker for neuroendocrine tumors. In this study we evaluate the expression of INSM1 in primary gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) and in their known metastases, in order to assess its sensitivity compared to chromogranin-A (CgA) and synaptophysin (SYN), and to evaluate for any change in expression between primary and metastatic disease.


We identified 30 patients with primary GEP-NEN. In 26 patients their liver metastatic tissue was available; two patients had two metachronous metastatic foci, yielding a total of 28 metastatic cases. Additional 2 and 7 non-paired cases of primary and metastatic grade-3 GEP-NEN respectively, were included. To evaluate for specificity, we evaluated the expression of these markers in other primary tumors (colorectal adenocarcinoma, acinar cell carcinoma, solid pseudopapillary neoplasm, cholangiocarcinoma, and hepatocellular carcinoma) and metastatic tumors in the liver (adrenal cortical, breast and prostate carcinomas) which may arise as a differential diagnoses. In our cohort, all the primary and 94% of the metastatic GEP-NEN expressed INSM1. INSM1 showed similar sensitivity to SYN and higher sensitivity compared to CgA, in both primary and metastatic neoplasms. INSM1 has comparable specificity to CgA, and higher than SYN.


The nuclear reactivity and the high sensitivity and specificity of INSM1 make it a preferred neuroendocrine marker. In conclusion, INSM1 can be used as a single first line marker for primary and metastatic GEP-NEN. This article is protected by copyright. All rights reserved.


INSM1; Neuroendocrine neoplasm; gastrointestinal tract; immunohistochemistry; pancreatobiliary tract


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