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Updated: May 11, 2026
Detection of G Protein-coupled Receptor Expression in Mouse Vagal Afferent Neurons using Multiplex In Situ Hybridization
Published on: September 20, 2021
A study of gata3 and phox2b expression in tumors of the autonomic nervous system
Daisuke Nonaka1, Beverly Y Wang, David Edmondson
1Department of Histopathology, The Christie Hospital, Christie NHS Foundation Trust, Wilmslow Road,Manchester, UK. dnonaka@msn.com
Abstract:
Autonomic neurons and chromaffin cells, which constitute the autonomic nervous system, are derived from a common progenitor from the neural crest, and its development is controlled by a network of transcription factors, including the master regulator, Phox2b, and its downstream, Gata3. Anti-Phox2b and anti-Gata3 antibodies were applied to a total of 77 autonomic nervous system tumors, including 35 paragangliomas, 21 pheochromocytomas, 9 neuroblastomas, 4 ganglioneuroblastomas, and 8 ganglioneuromas, as well as their potential morphologic mimics, including tumors of the small round cell tumor group, neuroendocrine carcinomas of lung and gastrointestinal tract (carcinoid tumors/neuroendocrine tumors, large cell neuroendocrine carcinomas, and small cell carcinomas), Merkel cell carcinomas, benign and malignant tumors of thyroid, parathyroid, and adrenal cortex, and malignant melanomas. A variety of nonendocrine/neuroendocrine carcinomas were also studied. Gata3 expression was seen in 89% of paragangliomas, 95% of pheochromocytomas, and all neuroblastomas, ganglioneuroblastomas, and ganglioneuromas, as well as in all parathyroid tumors, a majority of urothelial and mammary carcinomas, and a subset of squamous cell carcinomas, but all other tumors were negative. Phox2b expression was seen in all neuroblastomas, ganglioneuroblastomas, and ganglioneuromas and in 40% of paragangliomas, but pheochromocytomas and all other tumors were negative. Gata3 is a highly reliable marker for paragangliomas, pheochromocytomas, and neuroblastic tumors to distinguish from their simulators. This is an additional utility for this marker, which is used for the diagnosis of urothelial and mammary carcinomas. Phox2b is also highly specific, but its low sensitivity to paragangliomas and pheochromocytomas would limit the utility only to neuroblastic tumors.
Insights
Gata3 is a reliable marker for identifying paragangliomas, pheochromocytomas, and neuroblastic tumors, distinguishing them from mimics. Phox2b is specific but less sensitive for paragangliomas and pheochromocytomas, making it best for neuroblastic tumors.
Area of Science:
- Neuroscience
- Oncology
- Molecular Biology
Background:
- Autonomic nervous system tumors arise from neural crest progenitors.
- Transcription factors Phox2b and Gata3 regulate autonomic nervous system development.
- Distinguishing these tumors from mimics is clinically important.
Purpose of the Study:
- To evaluate the diagnostic utility of Phox2b and Gata3 expression in autonomic nervous system tumors and their mimics.
- To determine the sensitivity and specificity of these markers in various tumor types.
Main Methods:
- Immunohistochemical analysis using anti-Phox2b and anti-Gata3 antibodies.
- Study included 77 autonomic nervous system tumors (paragangliomas, pheochromocytomas, neuroblastomas, etc.) and various morphologic mimics.
- Analysis of expression patterns in tumor samples.
Main Results:
- Gata3 was expressed in 89% of paragangliomas, 95% of pheochromocytomas, and all neuroblastic tumors.
- Phox2b was expressed in all neuroblastic tumors and 40% of paragangliomas; it was negative in pheochromocytomas.
- Gata3 showed high reliability for paragangliomas, pheochromocytomas, and neuroblastic tumors; Phox2b was highly specific but less sensitive for paragangliomas/pheochromocytomas.
Conclusions:
- Gata3 is a valuable marker for differentiating paragangliomas, pheochromocytomas, and neuroblastic tumors from their simulators.
- Phox2b is a useful marker primarily for neuroblastic tumors due to its specificity but limited sensitivity for other tumor types.
