Islet 1 is a transcription factor encoded by ISL-1 gene in the LIM-homeodomain subfamily. It is involved in the embryogenesis and differentiation of beta cells within the islets of Langerhans and crucial for pancreatic and motor neuron development. Islet 1 represents a differentiation marker expressed in the pancreas within normal islet cells and has been proposed as a marker for pancreatic neuroendocrine tumors.

Islet 1 is a sensitive lineage-specific marker for pancreatic neuroendocrine neoplasms and their metastases. Sensitivity ranges from 69-90% for primary pancreatic neoplasms, and 67-76% for metastatic neoplasms. Islet 1 has also been reported in duodenal, colonic and rectal neuroendocrine neoplasms. Due to the difficulty in distinguishing the primary site from metastatic neuroendocrine tumors with histological features, addition of Islet 1 staining to a panel of immunohistochemistry markers (PAX8, TTF1, and CDX2) identified the correct primary site in 75% of metastatic cases, demonstrating significant improvement over the three antibody panel (67%). Addition of Islet 1 to an immunohistochemical panel would be a useful adjunct to determine the site of origin in metastatic neuroendocrine tumor of unknown primary.