Immunohistochemical analysis of OTP and NKX6.1 in neuroendocrine tumors of the lung and pancreas

Background: Homeobox transcription factors have demonstrated utility in diagnosing neuroendocrine tumors. Orthopedia homeobox protein (OTP) has a well-defined role in embryonic neurodevelopment and has also been described as a prognostic marker in lung neuroendocrine tumors (NET). Additionally, NK6 homeobox-1 (NKX6.1) has been described to be necessary for the development of neuroendocrine cells in the pancreas. We evaluated immunohistochemical (IHC) expression of OTP and NKX6.1 to determine their utility in the diagnosis of NETs from lung and pancreas fine-needle aspirations (FNA). Methods: Our study examined 50 FNA specimens, including 30 primary pulmonary NETs (8 carcinoid tumors (CT), 6 atypical carcinoids (AC), 11 small-cell neuroendocrine carcinomas (SCNEC), 5 large-cell neuroendocrine carcinomas (LCNEC)) and 20 primary pancreatic NETs (17 well-differentiated pancreatic neuroendocrine tumors (PanNET) and 3 poorly differentiated pancreatic neuroendocrine carcinomas (PanNEC)). IHC expression of OTP, NKX6.1, and Ki-67 was evaluated on FNA cell blocks. Results: Half of the pulmonary TC tumors expressed OTP, while only 17% of AC and 20% of LCNEC expressed OTP. Neither SCNECs nor any pancreatic NET expressed OTP. In contrast, intermediate and high-grade tumors expressed NKX6.1 (LCNEC-80%, SCNEC-82%, and AC-83%) more often than low-grade tumors (TC-63%, PanNET-71%). All three PanNECs expressed NKX6.1. Conclusions: OTP may be useful in diagnosing well-differentiated NETs of pulmonary origin. NKX6.1 may have utility in segregating high from low-grade NETs of both pulmonary and pancreatic origin, although other methods will be required to determine site of origin.