INSM1

 

Insulinoma-associated protein 1 (INSM1) is a zinc-finger transcription factor that plays a critical regulatory role in the development and differentiation of neuroendocrine cells. INSM1 expression is consistently detected in tissues exhibiting neuroendocrine differentiation. These include the medullary chromaffin cells of the adrenal gland, neuronal populations within embryonic cerebral cortex and cerebellum, enterochromaffin cells of the gastrointestinal tract, thymic medulla4, thyroid C-cells, and occasional cells from the adenohypophysis and pulmonary bronchus. Additionally, Merkel cells of the skin also demonstrate INSM1 immunoreactivity and weak positivity for INSM1 has been reported in scattered lymphocytes and ganglion cells. Although INSM1 is expressed in embryonic cerebellum and cerebrum, it is absent in terminally differentiated tissues. Similarly, it is present in pancreatic islet (Langerhans) cells but not in exocrine pancreas. No staining is observed in other normal tissues, including skin adnexa, adrenal cortex, breast, thyroid follicles, cardiac muscle, liver, kidney,
testis, and skeletal muscle.

Intended use

INSM1 is intended to be used as a differentiation marker for neuroendocrine tumor types. Recent studies suggest that INSM1 is a highly specific biomarker for neuroendocrine differentiation, demonstrating greater specificity
than chromogranin A (CGA) and comparable or superior sensitivity to synaptophysin (SYP) and CD56. INSM1 is detected in 75-100% of neoplastic cells of neuroendocrine neoplasms, including small cell lung carcinoma and medullary thyroid carcinoma. Studies have also shown that occasional, predominantly weaker INSM1 positivity may be observed in neoplastic cells of Hodgkin lymphoma, prostate adenocarcinoma, ovarian carcinoma, pancreatic adenocarcinoma, gastric carcinoma, lung squamous cell carcinoma, and breast
carcinoma. INSM1 expression is absent in 90-99% of lung adenocarcinomas, 86-100% of colorectal carcinomas, and 95-100% of melanomas.

Specifications
product code: 8379-C010	Clone: ZR395 [Mouse monoclonal]
Staining pattern: Nuclear staining	Control tissue:  Appendix, pancreas
Associated panels: Neuroendocrine
Assessment criteria
Neuroendocrine cells should show a moderate to strong staining reaction in the appendiceal mucosa, Columnar epithelial cells and smooth muscle cells in appendix should be negative.
A moderate to strong nuclear staining reaction should be seen in the endocrine cells in the islets of Langerhans in pancreas.
literature:
Mukhopadhyay S, Dermawan JK, Lanigan CP, Farver CF. Insulinoma-associated protein 1 (INSM1) is a sensitive and highly specific marker of neuroendocrine differentiation in primary lung neoplasms: an immunohistochemical study of 345 cases, including 292 whole-tissue sections. Mod Pathol. 2019; 32(1): 100-109.
Rooper LM, Sharma R, Li QK, Illei PB, Westra WH. INSM1 Demonstrates Superior Performance to the Individual and Combined Use of Synaptophysin, Chromogranin and CD56 for Diagnosing Neuroendocrine Tumors of the Thoracic Cavity. Am J Surg Pathol. 2017; 41(11): 1561-1569. https://doi.org/10.1097/pas.0000000000000916.