{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNKX2-1 is a master regulator of normal organ development whose pivotal functions have been demonstrated in the lung, thyroid, and brain. During embryogenesis it directs the differentiation of alveolar type II cells by controlling surfactant protein gene expression and, in the thyroid, it cooperates with other factors (such as FOXA1 and Pax8) to ensure tissue‐specific gene regulation. Mutations or haploinsufficiency of NKX2-1 result in congenital hypothyroidism, benign hereditary chorea, and the multisystem brain–lung–thyroid syndrome, underscoring its fundamental role in early cell‐fate specification and organogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer, NKX2-1 exhibits complex, dual roles. In lung adenocarcinoma and T-cell acute lymphoblastic leukemia, its persistent expression often serves as a lineage-survival oncogene that promotes proliferation and sustains pro-survival signaling (for example, via induction of ROR1). Conversely, its downregulation or loss is associated with tumor dedifferentiation, enhanced metastatic seeding via promotion of epithelial-to-mesenchymal transition, and lineage plasticity that gives rise to alternative – even gastrointestinal – differentiation programs. In these ways, NKX2-1 can both drive tumor growth and, when reduced, remove differentiation constraints that limit malignant progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its biological role, NKX2-1 (often referred to as thyroid transcription factor‑1 or TTF-1) is widely exploited as a diagnostic and prognostic biomarker in clinical oncology. Its expression—or aberrant gene amplification—in lung carcinomas reliably distinguishes primary adenocarcinomas from squamous and metastatic tumors and contributes to patient stratification for targeted therapies and assessments of circulating tumor cells. NKX2-1 immunostaining is also used to evaluate neuroendocrine and gynecologic neoplasms, thereby enhancing diagnostic accuracy and guiding treatment decisions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Joachim Pohlenz, Alexandra Dumitrescu, Dorothee Zundel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Partial deficiency of thyroid transcription factor 1 produces predominantly neurological defects in humans and mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI14192"}], "href": "https://doi.org/10.1172/JCI14192"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11854318"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11854318"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Heiko Krude, Barbara Schütz, Heike Biebermann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI14341"}], "href": "https://doi.org/10.1172/JCI14341"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11854319"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11854319"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nathalie Sturm, Giulio Rossi, Sylvie Lantuejoul, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of thyroid transcription factor-1 in the spectrum of neuroendocrine cell lung proliferations with special interest in carcinoids."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Pathol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/hupa.2002.31299"}], "href": "https://doi.org/10.1053/hupa.2002.31299"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11957142"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11957142"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Guido J Breedveld, Jeroen W F van Dongen, Cesare Danesino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in TITF-1 are associated with benign hereditary chorea."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/11.8.971"}], "href": "https://doi.org/10.1093/hmg/11.8.971"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11971878"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11971878"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Tina Di Palma, Roberto Nitsch, Anna Mascia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The paired domain-containing factor Pax8 and the homeodomain-containing factor TTF-1 directly interact and synergistically activate transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M205977200"}], "href": "https://doi.org/10.1074/jbc.M205977200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12441357"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12441357"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Venkatadri Kolla, Linda W Gonzales, John Gonzales, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thyroid transcription factor in differentiating type II cells: regulation, isoforms, and target genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Cell Mol Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1165/rcmb.2006-0207OC"}], "href": "https://doi.org/10.1165/rcmb.2006-0207OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16960125"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16960125"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Parviz Minoo, Lingyan Hu, Yiming Xing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Physical and functional interactions between homeodomain NKX2.1 and winged helix/forkhead FOXA1 in lung epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01133-06"}], "href": "https://doi.org/10.1128/MCB.01133-06"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17220277"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17220277"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Elly S W Ngan, Brian H H Lang, Tingting Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A germline mutation (A339V) in thyroid transcription factor-1 (TITF-1/NKX2.1) in patients with multinodular goiter and papillary thyroid carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Natl Cancer Inst (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jnci/djn471"}], "href": "https://doi.org/10.1093/jnci/djn471"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19176457"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19176457"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Aurore Carré, Gabor Szinnai, Mireille Castanet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Five new TTF1/NKX2.1 mutations in brain-lung-thyroid syndrome: rescue by PAX8 synergism in one case."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddp162"}], "href": "https://doi.org/10.1093/hmg/ddp162"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19336474"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19336474"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Satoshi Narumi, Koji Muroya, Yumi Asakura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcription factor mutations and congenital hypothyroidism: systematic genetic screening of a population-based cohort of Japanese patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2009-2373"}], "href": "https://doi.org/10.1210/jc.2009-2373"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20157192"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20157192"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Adam L Goulburn, Darym Alden, Richard P Davis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A targeted NKX2.1 human embryonic stem cell reporter line enables identification of human basal forebrain derivatives."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/stem.587"}], "href": "https://doi.org/10.1002/stem.587"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21425409"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21425409"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Domitille Gras, Laurence Jonard, Emmanuel Roze, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Benign hereditary chorea: phenotype, prognosis, therapeutic outcome and long term follow-up in a large series with new mutations in the TITF1/NKX2-1 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurol Neurosurg Psychiatry (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jnnp-2012-302505"}], "href": "https://doi.org/10.1136/jnnp-2012-302505"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22832740"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22832740"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Hisaaki Tanaka, Kiyoshi Yanagisawa, Keiko Shinjo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lineage-specific dependency of lung adenocarcinomas on the lung development regulator TTF-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-06-4774"}], "href": "https://doi.org/10.1158/0008-5472.CAN-06-4774"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17616654"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17616654"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "K A Kwei, Y H Kim, L Girard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genomic profiling identifies TITF1 as a lineage-specific oncogene amplified in lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1211012"}], "href": "https://doi.org/10.1038/sj.onc.1211012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18212743"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18212743"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Justine A Barletta, Sven Perner, A John Iafrate, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical significance of TTF-1 protein expression and TTF-1 gene amplification in lung adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1582-4934.2008.00594.x"}], "href": "https://doi.org/10.1111/j.1582-4934.2008.00594.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19040416"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19040416"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Roy-Akira Saito, Tetsuro Watabe, Kana Horiguchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thyroid transcription factor-1 inhibits transforming growth factor-beta-mediated epithelial-to-mesenchymal transition in lung adenocarcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-08-3490"}], "href": "https://doi.org/10.1158/0008-5472.CAN-08-3490"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19293183"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19293183"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Loïc Guillot, Aurore Carré, Gabor Szinnai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NKX2-1 mutations leading to surfactant protein promoter dysregulation cause interstitial lung disease in \"Brain-Lung-Thyroid Syndrome\"."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.21183"}], "href": "https://doi.org/10.1002/humu.21183"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20020530"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20020530"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Monte M Winslow, Talya L Dayton, Roel G W Verhaak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Suppression of lung adenocarcinoma progression by Nkx2-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09881"}], "href": "https://doi.org/10.1038/nature09881"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21471965"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21471965"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Irene Homminga, Rob Pieters, Anton W Langerak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integrated transcript and genome analyses reveal NKX2-1 and MEF2C as potential oncogenes in T cell acute lymphoblastic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2011.02.008"}], "href": "https://doi.org/10.1016/j.ccr.2011.02.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21481790"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21481790"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Tomoya Yamaguchi, Kiyoshi Yanagisawa, Ryoji Sugiyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NKX2-1/TITF1/TTF-1-Induced ROR1 is required to sustain EGFR survival signaling in lung adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2012.02.008"}], "href": "https://doi.org/10.1016/j.ccr.2012.02.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22439932"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22439932"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "David H Hwang, Lynette M Sholl, Vanesa Rojas-Rudilla, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KRAS and NKX2-1 Mutations in Invasive Mucinous Adenocarcinoma of the Lung."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thorac Oncol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jtho.2016.01.010"}], "href": "https://doi.org/10.1016/j.jtho.2016.01.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26829311"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26829311"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Purushothama Rao Tata, Ryan D Chow, Srinivas Vinod Saladi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Developmental History Provides a Roadmap for the Emergence of Tumor Plasticity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2018.02.024"}], "href": "https://doi.org/10.1016/j.devcel.2018.02.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29587142"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29587142"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "T Berghmans, M Paesmans, C Mascaux, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thyroid transcription factor 1--a new prognostic factor in lung cancer: a meta-analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Oncol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/annonc/mdl287"}], "href": "https://doi.org/10.1093/annonc/mdl287"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16980598"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16980598"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Koushan Siami, W Glenn McCluggage, Nelson G Ordonez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thyroid transcription factor-1 expression in endometrial and endocervical adenocarcinomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Surg Pathol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/PAS.0b013e3181131e21"}], "href": "https://doi.org/10.1097/PAS.0b013e3181131e21"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18059234"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18059234"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Lena A Kubba, W Glenn McCluggage, Jinsong Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thyroid transcription factor-1 expression in ovarian epithelial neoplasms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mod Pathol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/modpathol.2008.4"}], "href": "https://doi.org/10.1038/modpathol.2008.4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18246044"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18246044"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Giovanni Zito, Pierina Richiusa, Alessandra Bommarito, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In vitro identification and characterization of CD133(pos) cancer stem-like cells in anaplastic thyroid carcinoma cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0003544"}], "href": "https://doi.org/10.1371/journal.pone.0003544"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18958156"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18958156"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Paul J Zhang, Hong G Gao, Theresa L Pasha, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TTF-1 expression in ovarian and uterine epithelial neoplasia and its potential significance, an immunohistochemical assessment with multiple monoclonal antibodies and different secondary detection systems."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Gynecol Pathol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/PGP.0b013e3181804bc6"}], "href": "https://doi.org/10.1097/PGP.0b013e3181804bc6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19047914"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19047914"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Valsamo K Anagnostou, Konstantinos N Syrigos, Gerold Bepler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thyroid transcription factor 1 is an independent prognostic factor for patients with stage I lung adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Oncol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1200/JCO.2008.17.0043"}], "href": "https://doi.org/10.1200/JCO.2008.17.0043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19064983"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19064983"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Justin A Bishop, Rajni Sharma, Peter B Illei "}, {"type": "b", "children": [{"type": "t", "text": "Napsin A and thyroid transcription factor-1 expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Pathol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.humpath.2009.06.014"}], "href": "https://doi.org/10.1016/j.humpath.2009.06.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19740516"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19740516"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "W Glenn McCluggage, Kathryn Kennedy, Klaus J Busam "}, {"type": "b", "children": [{"type": "t", "text": "An immunohistochemical study of cervical neuroendocrine carcinomas: Neoplasms that are commonly TTF1 positive and which may express CK20 and P63."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Surg Pathol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/PAS.0b013e3181d1d457"}], "href": "https://doi.org/10.1097/PAS.0b013e3181d1d457"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20182342"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20182342"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Sun Och Yoon, Young Tae Kim, Kyeong Cheon Jung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TTF-1 mRNA-positive circulating tumor cells in the peripheral blood predict poor prognosis in surgically resected non-small cell lung cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lung Cancer (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.lungcan.2010.04.017"}], "href": "https://doi.org/10.1016/j.lungcan.2010.04.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20471712"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20471712"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Lisa M Stoll, Michael W Johnson, Edward Gabrielson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The utility of napsin-A in the identification of primary and metastatic lung adenocarcinoma among cytologically poorly differentiated carcinomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cytopathol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cncy.20108"}], "href": "https://doi.org/10.1002/cncy.20108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20830690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20830690"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Akihiko Yoshida, Koji Tsuta, Shun-ichi Watanabe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Frequent ALK rearrangement and TTF-1/p63 co-expression in lung adenocarcinoma with signet-ring cell component."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lung Cancer (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.lungcan.2010.09.013"}], "href": "https://doi.org/10.1016/j.lungcan.2010.09.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21036415"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21036415"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Sanjay Mukhopadhyay, Anna-Luise A Katzenstein "}, {"type": "b", "children": [{"type": "t", "text": "Subclassification of non-small cell lung carcinomas lacking morphologic differentiation on biopsy specimens: Utility of an immunohistochemical panel containing TTF-1, napsin A, p63, and CK5/6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Surg Pathol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/PAS.0b013e3182036d05"}], "href": "https://doi.org/10.1097/PAS.0b013e3182036d05"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21164283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21164283"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Jiqing Ye, Jennifer J Findeis-Hosey, Qi Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Combination of napsin A and TTF-1 immunohistochemistry helps in differentiating primary lung adenocarcinoma from metastatic carcinoma in the lung."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Appl Immunohistochem Mol Morphol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/PAI.0b013e318205b059"}], "href": "https://doi.org/10.1097/PAI.0b013e318205b059"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21464700"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21464700"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Jong-Mu Sun, Joungho Han, Jin Seok Ahn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Significance of thymidylate synthase and thyroid transcription factor 1 expression in patients with nonsquamous non-small cell lung cancer treated with pemetrexed-based chemotherapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thorac Oncol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/JTO.0b013e3182208ea8"}], "href": "https://doi.org/10.1097/JTO.0b013e3182208ea8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21716147"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21716147"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Tomoya Yamaguchi, Yasuyuki Hosono, Kiyoshi Yanagisawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NKX2-1/TTF-1: an enigmatic oncogene that functions as a double-edged sword for cancer cell survival and progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2013.04.002"}], "href": "https://doi.org/10.1016/j.ccr.2013.04.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23763999"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23763999"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Arne Warth, Roland Penzel, Heike Lindenmaier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EGFR, KRAS, BRAF and ALK gene alterations in lung adenocarcinomas: patient outcome, interplay with morphology and immunophenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Respir J (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1183/09031936.00018013"}], "href": "https://doi.org/10.1183/09031936.00018013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23988776"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23988776"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Jennifer Pors, Angela Cheng, Joyce M Leo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Comparison of GATA3, TTF1, CD10, and Calretinin in Identifying Mesonephric and Mesonephric-like Carcinomas of the Gynecologic Tract."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Surg Pathol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/PAS.0000000000001142"}], "href": "https://doi.org/10.1097/PAS.0000000000001142"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30148742"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30148742"}]}]}]}