Journal
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Volume 77, Issue 5, Pages 374-382Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/jnen/nly014
Keywords
Biomarker; Immunohistochemistry; INSM1; Medulloblastoma; Neurodevelopment; Neuroendocrine
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Funding
- National Institutes of Health NINDS [R25 NS079185, R01 NS096754, R01 NS055089]
- Alex's Lemonade Stand Foundation for Childhood Cancer
- Childhood Brain Tumor Foundation
- Pilocytic/Pilomyxoid Astrocytoma Fund
- Lauren's First Goal
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Tumors with a neuronal component comprise a small percentage of central nervous system (CNS) neoplasms overall, but the presence of neuronal differentiation has important diagnostic, prognostic, and therapeutic implications. Insulinoma-associated protein 1 (INSM1) is a transcription factor with strong nuclear immunostaining in neuroendocrine cells and neoplasms of neuroendocrine origin; however, its expression in the CNS in normal brain and in neoplastic cells has not been fully explored. Here, we present immunostaining results from a large number of archival CNS tissue specimens, including 416 tumors. Nuclear immunostaining for INSM1 was frequently seen in medulloblastomas (87%, n = 94). Diffuse nuclear INSM1 immunostaining was detected in all central neurocytomas and pituitary adenomas. Patchy to rare staining with INSM1 was also seen in other high-grade embryonal tumors and high-grade gliomas. In normal brain tissue, specific nuclear INSM1 immunohistochemical staining was only seen in early neuronal development. Notably, nuclear INSM1 staining was not seen in adult normal brain, including areas of gliosis. These findings indicate that nuclear INSM1 immunostaining may serve as a strong nuclear marker in the brain for neoplasms of neuroendocrine or immature neuronal differentiation, when used in concert with other immunostains.
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