NKX2-1 (also known as thyroid transcription factor TTF-1) is a nuclear protein involved in the differentiation of lung, thyroid and forebrain cells. It regulates the expression of surfactant proteins in the lung that are required for host defense and stability. TTF-1 is a useful marker for distinguishing a primary lung adenocarcinoma from metastases, particularly when combined with Napsin A in a marker panel. In normal tissues, it is expressed in Type II pneumocytes, Clara Cells, thyroid follicular epithelium and parafollicular C cells. NKX2-1 antibodies are useful for distinguishing primary pulmonary adenocarcinoma (positive staining) from metastases, pleural lung carcinomas (positive) from mesotheliomas, and also small cell carcinoma of the lung (positive) from Merkel cell carcinoma. NKX2-1 is positive in small cell lung carcinomas, adenocarcinomas, thyroid hyperplasias and carcinomas, and neoplasias. It is expected to have nuclear staining. References: Clin Sci. 2009 Jan. 116.1; 27-35, PMID: 19037882; Clin Onc. 2009 Jan. 27.2; 271-278, DOI:10.1200/JCO.2008.17.0043; AIMM 2002 10(2):97; Annals of Oncology 2006 17(11):1672; Am J Surg path 2001 25:363; Mod path 2000 13:570