Insulinoma-associated protein 1 expression in primary and metastatic neuroendocrine neoplasms of the gastrointestinal and pancreaticobiliary tracts

Aims: Insulinoma-associated protein 1 (INSM1) is a transcription factor that is expressed in developing and mature neuroendocrine tissue. Recent studies have shown that INSM1 is a sensitive marker for neuroendocrine tumours. The aims of this study were to evaluate INSM1 expression in primary gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) and in their known metastases, in order to assess its sensitivity as compared with chromogranin-A (CgA) and synaptophysin (SYN), and to evaluate any change in expression between primary and metastatic disease. Methods and results: We identified 30 patients with primary GEP-NEN. Liver metastatic tissue was available for 26 patients; two patients had two metachronous metastatic foci, yielding a total of 28 metastatic cases. An additional two and seven non-paired cases of primary and metastatic grade 3 GEP-NEN, respectively, were included. To assess specificity, we evaluated the expression of these markers in other primary tumours (colorectal adenocarcinoma, acinar cell carcinoma, solid pseudopapillary neoplasm, cholangiocarcinoma, and hepatocellular carcinoma) and metastatic tumours in the liver (adrenal cortical, breast and prostate carcinomas) that may present as differential diagnoses. In our cohort, all of the primary GEP-NENs and 94% of the metastatic GEP-NENs expressed INSM1. INSM1 showed similar sensitivity to SYN and higher sensitivity than CgA in both primary and metastatic neoplasms. INSM1 has comparable specificity to CgA, and higher specificity than SYN. Conclusions: 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.