TTF-1 / Thyroid Transcription Factor 1 / NKX2-1 (MSVA-312R)

Recombinant Rabbit monoclonal / IgG 1:100 – 1:200 Research Use Only Nucleus Human MSVA-312R BCH, Benign chorea, BHC, Homeobox protein Nkx2.1, NK2 homeobox 1, NKX2.1, NKX2A, TEBP, Thyroid nuclear factor-1, Thyroid specific enhancer binding protein, Thyroid transcription factor-1 (TTF-1), Tin man, TITF1, TTF-1 Lung: Nuclear TTF1 staining should be strong in pneumocytes and in basal cells of the terminal bronchioles while a weaker, still moderate to strong staining should be seen in columnar epithelial cells of the terminal bronchioles (low expressor control). Liver: TTF1 staining must not be seen in any cells. TTF-1 is a protein with high specificity for lung and thyroid. Thyroid transcription factor-1 (TTF1), also termed NK2 homeobox 1 ( NKX2-1 ) is a 38 kDa nuclear protein encoded by the NKX2-1 gene at chromosome 14q13 . TTF1 has a critical role in morphogenesis of the thyroid, the lung and the diencephalon where it acts as a tissue-specific transcription promoter. Blocking TTF1 gene expression results in developmental defects of thyroid, lung and brain. In the thyroid gland, TTF1 induces the expression of thyroglobulin, thyroperoxidase and thyrotropin receptor. In the lung, TTF1 promotes the transcription of the surfactant proteins A to D, and the Clara cell secretory protein. Among normal tissues, TTF1 expression is restricted to the respiratory system, thyroid, pituitary gland, and the thalamus. Among cancers, TTF1 expression is particularly common in thyroid cancer, pulmonary adenocarcinoma, pulmonary small cell carcinomas, as well as in small cell carcinomas from other sites of origin. Less commonly, TTF1 positivity is also seen in other tumor en... Images describing the TTF1 staining pattern in normal tissues obtained by the antibody MSVA-312R are shown in our “ Normal Tissue Gallery ”. Brain Cerebrum Negative. Cerebellum Negative. Endocrine Tissues Thyroid StrongTTF1 staining of all follicular epithelial cells. Parathyroid Negative. Adrenal gland Negative. Pituitary gland StrongTTF1 staining of pituicytes. Respiratory system Respiratory epithelium Strong TTF1 staining of respiratory epithelial cells, especially of basal cells in bronchial mucosa. TTF1 staining is much weaker or absent in respiratory epithelial cells of paranasal sinus. Weak to moderate TTF1 positivity of mucinous cells in bronchial glands. Lung Strong TTF1 staining of pneumocytes. Gastrointestinal Tract Salivary glands Negative. Esophagus Negative. Stomach Negative. Duodenum Negative. Small intestine Negative. Appendix Negative. Colon Negative. Rectum Negative. Liver Negative. Gallbladder Negative. Pancreas Negative. Genitourinary Kidney Negative. Urothelium Neg... Among thyroid cancers, TTF1 is seen in virtually all tumors derived from follicular cells (i.e. follicular adenoma, follicular and papillary carcinoma). C-cell derived medullary carcinomas are mostly TTF1 positive while anaplastic thyroid carcinomas are usually negative. Among lung cancers, adenocarcinomas are positive in 60-85% but mucinous adenocarcinomas are more often negative. Small cell carcinomas of the lung are TTF1 positive in >90% of cases but extrapulmonary small cell carcinomas are also often positive (>40%). TTF1 positivity is (rarely) also seen in other tumor entities including colorectal, endometrial and stomach cancers. The TCGA findings on TTF-1 RNA expression in different tumor categories have been summarized in the Human Protein Atlas. TTF1 negative malignant mesothelioma (epitheloid). (2) Papillary carcinoma with strong TTF1 positivity of all tumor cells TTF1 negative squamous cell carcinoma Cancer tissue gallery TTF ‐ 1 (MSVA-312R ) publication summary Relevant publication: Möller et al. “TTF‐1 is a highly sensitive but not fully specific marker for pulmonary and thyroidal cancer: a tissue microarray study evaluating more than 17,000 tumors from 152 different tumor entities.” Published in Virchows Archive 2024 Oct 8. Epub ahead of print. PMID: 39377914. A total of 15’564 tumors from 152 different tumor categories were successfully analyzed by using the following protocol:  Heat-induced antigen retrieval for 5 minutes in an autoclave at 121°C in a pH 9 Target Retrieval Solution buffer. MSVA-312R at a dilution of 1:150 at 37°C for 60 minutes. Visualization of bound antibody by the EnVision Kit (Dako, Agilent). This protocol was also used for all stainings depicted in our tumor and normal tissue galleries. Overall, 82 of 152 tumor categories showed detectable TTF1 expression in at least one case and 42 tumor categories included at least one case with strong TTF1 positivity. By far the highest pos... IHC users have different preferences on how the stains should look like. Some prefer high staining intensity of the target stain and even accept some background. Others favor absolute specificity and lighter target stains. Factors that invariably lead to more intense staining include higher concentration of the antibody and visualization tools, longer incubation time, higher temperature during incubation, higher temperature and longer duration of the heat induced epitope retrieval (slide pretreatment). The impact of the pH during slide pretreatment has variable effects and depends on the antibody and the target protein. All images and data shown here and in our image galleries are obtained by the manual protocol described below. Other protocols resulting in equivalent staining are described as well. Manual protocol Freshly cut sections should be used (less than 10 days between cutting and staining). Heat-induced antigen retrieval for 5 minutes in an autoclave at 121°C in pH 7,8 Target ... Distinction of lung adenocarcinoma (usually positive) from metastasis to the lung (usually negative) and pleural mesothelioma (negative). Distinction of Merkel cell carcinoma (usually negative) from metastatic small cell carcinoma of the lung (mostly positive) There are two ways how the specificity of antibodies can be documented for immunohistochemistry on formalin fixed tissues. These are: 1. Comparison with a second independent method for target expression measurement across a large number of different tissue types (orthogonal strategy), and 2. Comparison with one or several independent antibodies for the same target and showing that all positive staining results are also seen with other antibodies for the same target (independent antibody strategy). Orthogonal validation: For the antibody MSVA-312R specificity is suggested by the complete concordance of the immunostaining data with data from three independent RNA screening studies, including the Human Protein Atlas (HPA) RNA-seq tissue dataset, the FANTOM5 project, and the Genotype-Tissue Expression (GTEx) project, which are all summarized in the Human Protein Atlas (Tissue expression TTF-1) . TTF1 immunostaining by MSVA-312R was only seen in the three tissues, for which RNA expression h...