Abstract
Background: Insulinoma-associated protein 1 (INSM1) has been considered as a novel immunostain for neuroendocrine tumors (NETs) and is hypothesized to be more reliable than first-generation NET biomarkers, such as CGA (chromogranin A), SYP (synaptophysin) and CD56 (neural cell adhesion molecule). In this review, we summarize existing literature on INSM1′s reliability as an immunostain for detection of various NETs, its results in comparison to first-generation NET biomarkers, and its expression in both non-NETs and benign tissues/cells on cytology specimens (cell blocks/smears).
Highlights
In 1992, a subtraction library was constructed from rare human insulinoma and glucagonoma tissues [1] to unveil the specific antigens associated with insulinoma and/or antigens that encode autoantigens in type 1 diabetes
In the head and neck area, sinonasal neuroendocrine carcinoma, neuroendocrine carcinomas localized in the hypopharynx larynx trachea and parapharyngeal space as well as HPV-related neuroendocrine carcinomas, paraganglioma and medullary thyroid carcinoma, are shown to be immunoreactive for Insulinoma-associated protein 1 (INSM1)
In the head and neck area, sinonasal neuroendocrine carcinoma and neuroendocrine carcinomas localized in the hypopharynx, larynx, trachea, and parapharyngeal space represent primary entities, while secondary neuroendocrine neoplasms can be detected in lymph nodes or soft tissue
Summary
In 1992, a subtraction library was constructed from rare human insulinoma and glucagonoma tissues [1] to unveil the specific antigens associated with insulinoma and/or antigens that encode autoantigens in type 1 diabetes. INSM1 is a protein that plays a cardinal role as a transcription factor in the differentiation of embryonic neuroendocrine cells. Numerous studies have demonstrated how INSM1 plays a crucial role in neuroendocrine differentiation in both neoplastic and normal pancreatic endocrine tissues. INSM1 was the ITF shown to be directly responsible in coordinating this conversion into insulin-positive cells, while the addition of the other two ITFs increased the efficiency of this trans-differentiation [6]. These results were replicated when tested in the Panc-1 (ATCC) cell line [7]. One functional role of INSM1 is as a repressor in the transcriptional network of the endocrine pancreas to coordinate differentiation into β-cells. This review will elucidate the clinical application of INSM1 as a nuclear biomarker of various NETs, and briefly discuss its expression in non-neoplastic tissues on cytologic material from cytopathologists’ points of view
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