Synonyms: Insulinoma-associated protein 1
by Jan Klos
Background
Insulinoma-associated protein 1 (INSM1) is coded by the gen with the same name INSM1. The protein functions as a repressor of transcription which regulates entry into cell cycle and controls neuroendocrine differentiation. It is a sensitive marker for neuroendocrine differentiation considered more sensitive and more specific than Synaptophysin, Chromogranin A or CD56. It is considered a potential neuroendocrine biomarker for the development of novel cancer therapeutics against neuroendocrine tumors.
Positivity in normal tissues
All neuroendocrine cells except parathyroid gland.
Positivity in tumors
All tumors with neuroendocrine differentiation except parathyroid tumors. Reactivity is present in circa 90% extraskeletal myxoid chondrosarcomas (with rearrangements of the NR4A3 gene), providing strong evidence for neuroendocrine differentiation. Potential pitfall are INSM1-positive tumors without evidence of neuroendocrine differentiation like Ewing sarcoma (30 %+), ossifying fibromyxoid tumor (30 %+), chordoma (10 % +), soft tissue myoepithelioma (5 %+). Basal cell carcinoma of the skin which stains positive with Chromogranin A in >70% is negative for INSM1, may be interpreted as argument against wide neuroendocrine differentiation in these tumors.
Staining pattern
Nuclear
Antibody clone
A8
Control tissue
Application
- Sensitive and specific marker for identification of neuroendocrine phenotype in normal and neoplastic tissues and immature neuronal differentiation in central nervous system
- High expression seems to be a negative prognostic indicator in neuroendocrine neoplasms in gastro-intestinal tract and positive prognostic indicator in small cell carcinomas of the lung.
Selected references
- Yoshida A,1,2 Makise N,1,3 Wakai S,1 et al. INSM1 expression and its diagnostic significance in extraskeletal myxoid chondrosarcoma Mod Pathol. 2018 May; 31(5):744-752. doi: 10.1038/modpathol.2017.189. Epub 2018 Jan 12. PMID: 29327709
- Lan MS, Breslin MB. Structure, expression, and biological function of INSM1 transcription factor in neuroendocrine differentiation FASEB J. 2009 Jul;23(7):2024-33. doi: 10.1096/fj.08-125971. Epub 2009 Feb 26. PMID: 19246490 PMCID: PMC 2704596
- Houcine Y 1, Chelly I 1,Zehani A 1, et al. Neuroendocrine differentiation in basal cell carcinoma. J Immunoassay Immunochem. 2017;38(5):487-493. doi: 10.1080/15321819.2017.1331170. Epub 2017 May 26. PMID: 28548901