A Study of Phox2b and Gata3 Expression in Tumors of Autonomic Nervous System Derivation
Daisuke Nonaka, Beverly Y Wang, Chen-Chih J Sun. Christie Hospital and the University of Manchester, Manchester, United Kingdom; Albert Einstein College of Medicine and Beth Israel Medical Center, New York, NY; University of Maryland School of Medicine and University of Maryland Medical Center, Baltimore, MD
Background: The sympathetic, parasympathetic and enteric ganglia, and adrenal medulla and extraadrenal paraganglia constitute the autonomic nervous system (ANS). Autonomic neurons and chromaffin cells are derived from a common progenitor from neural crest, and its development is controlled by a network of transcription factors (TFs), including the master regulator, Phox2b, and its downstream Gata3. Immunohistochemical expression of these two TFs has scarcely been studied in ANS- derived tumors.
Design: Anti-Phox2b and Gata-3 antibodies were applied to a total of 77 ANS tumors, including 35 paragangliomas, 21 pheochromocytomas, 9 neuroblastomas, 4 ganglioneuroblastomas, and 8 ganglioneuromas, as well as their potential morphologic mimickers, including 46 tumors of small round cell tumor group, such as olfactory neuroblastomas, rhabdomyosarcomas, germ cell tumors, Ewing sarcoma/PNET, and diffuse large B cell lymphomas, 127 neuroendocrine carcinomas of lung and GI (89 carcinoid tumors/NET, 11 large cell neuroendocrine carcinomas, and 27 small cell carcinomas), 26 Merkel cell carcinomas, 97 tumors of thyroid, parathyroid, and adrenal cortex, and 10 melanomas. The extent of staining was graded as focal (5-50%) and diffuse (50-100%).
Results: Gata3 expression was seen in 31/35 (89%) paragangliomas (25 diffuse, 6 focal), 20/21 (95%) pheochromocytomas (18 diffuse, 2 focal), and all neuroblastomas, ganglioneuroblastomas, and ganglioneuromas (all diffuse) while all other tumors were negative, except for 7 parathyroid tumors (2 carcinomas, 5 adenomas), which were all diffusely positive. Phox2b expression was seen in 14/35 (40%) paragangliomas (11 diffuse, 3 focal), none of pheochromocytomas, and all neuroblastomas, ganglioneuroblastomas, and ganglioneuromas (all diffuse except for 1 ganglioneuroma with focal staining) whereas all other tumors were negative.
Conclusions: Gata3 is a highly reliable marker for paragangliomas/pheochromocytomas and neuroblastic tumors to distinguish from their mimickers. 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/pheochromocytomas would limit the utility only to neuroblastic tumors.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 58, Wednesday Afternoon