Stains & molecular markers
TTF1


Topic Completed: 16 September 2020

Minor changes: 25 September 2020

Copyright: 2003-2020, PathologyOutlines.com, Inc.

PubMed Search: TTF1[TI] free full text[SB] pathology

Veronica Ulici, M.D., Ph.D.
Li Juan Wang, M.D., Ph.D.
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Cite this page: Ulici V, Wang LJ. TTF1. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainsttf1.html. Accessed September 26th, 2020.
Definition / general
  • Thyroid transcription factor 1, also known as NKX2-1 or thyroid specific enhancer binding protein
  • Homeodomain containing transcription factor, member of the NKX2 gene family (EMBO J 1990;9:3631)
  • Preferentially expressed in thyroid, lung and brain structures of diencephalic origin (Mod Pathol 2000;13:238, Development 1991;113:1093)
  • Different sensitivities for diverse neoplasms depending on the antibody clone used (Appl Immunohistochem Mol Morphol 2010;18:142, Am J Clin Pathol 2018;150:533)
    • Highly specific clone 8G7G3/1 is well suited to thyroid and lung
    • Highly sensitive clones SPT24 and SP141 are recommended for lung tumors, however their low specificity may produce aberrant staining in unusual locations
Essential features
  • Nuclear marker with preferential expression in thyroid, lung and brain structures of diencephalic origin
  • 2 commonly used commercially available clones and a novel clone with different sensitivities and specificities for pulmonary and extrapulmonary neoplasms
  • Expressed in a high percentage of lung adenocarcinoma and small cell carcinoma, also in a variable percentage of extrapulmonary small cell carcinoma
  • Consistently expressed in a wide range of differentiated thyroid tumors
  • Expressed in a number of CNS tumors such as chordoid glioma and subependymal giant cell astrocytoma
Terminology
  • NK2 homeobox 1 (official symbol: NKX2-1; gene ID: 7080), TITF1, T/EBP
  • Do not confuse with transcription termination factor 1 (official symbol: TTF1, an essential protein responsible for terminating ribosomal gene transcription that is encoded by the TTF1 gene in humans; gene ID: 7270) (EMBO J 1990;9:3631, Mol Cell Biol 1991;11:4927)
Pathophysiology
Clinical features
Interpretation
  • Exclusively nuclear stain
Uses by pathologists
Prognostic factors
Microscopic (histologic) images

Contributed by Li Juan Wang, M.D., Ph.D.

Nonneoplastic lung

Nonneoplastic thyroid follicles

Lung small cell carcinoma

Lung adenocarcinoma


Papillary thyroid carcinoma

Medullary thyroid carcinoma

Rectal small cell carcinoma

Bladder invasive urothelial carcinoma



Contributed by Andrey Bychkov, M.D., Ph.D. and Carolyn Glass, M.D.

Lung adenocarcinoma

Lung small cell carcinoma

Positive staining - normal
Positive staining - disease
Negative staining
Board review style question #1

Which set of results favors a primary lung adenocarcinoma as a source of tumor in a brain biopsy?

  1. TTF1 positive, CK7 positive, CK20 negative, napsin A positive
  2. TTF1 positive, CK7 positive, CK20 positive, GATA3 positive
  3. TTF1 positive, CK7 positive, PAX8 positive
  4. TTF1 positive, EMA positive, GFAP positive
Board review answer #1
A. TTF1 positive, CK7 positive, CK20 negative, napsin A positive

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Reference: TTF1
Board review style question #2
A 72 year old man presents with a neck mass, which shows sheets of small to medium sized cells with high N:C ratio, round / oval nuclei, finely dispersed chromatin (salt and pepper), indistinct nucleoli and scant cytoplasm. The tumor cells are positive for keratin, synaptophysin, chromogranin, CK20 (dot-like) and Ki67 proliferation index is 80%. The tumor cells are negative for CK7, TTF1, CDX2, calcitonin, melan A and S100. Which of the following is the most likely diagnosis of this tumor?

  1. Metastatic high grade neuroendocrine carcinoma from gastrointestinal tract
  2. Metastatic Merkel cell carcinoma
  3. Metastatic small cell carcinoma of lung
  4. Metastatic small cell melanoma
Board review answer #2
B. Metastatic Merkel cell carcinoma

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Reference: TTF1
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