Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 2 November 2015, last major update June 2005
Copyright: (c) 2003-2015,, Inc.
PubMed Search: TTF1[title]
Definition / General
  • Thyroid transcription factor, also called thyroid specific enhancer binding protein
  • 38 kDa nuclear protein that regulates transcription activity of thyroid (thyroglobulin, thyroperoxidase, sodium-iodide transport protein, calcitonin and MHC class I), lung (surfactant proteins A, B and C, Clara cell secretory protein) and diencephalon specific genes
  • Mutations cause pulmonary hypoplasia and neonatal death
  • Specificity depends on antibody clone used
  • Interpretation: nuclear stain
Uses by Pathologists
  • Distinguish primary (TTF1+) vs. metastatic (usually TTF1-) lung carcinoma
  • Distinguish pulmonary adenocarcinoma (TTF1+) from squamous cell carcinoma (usually TTF1-)
  • Pleural lung carcinoma (TTF1+) vs. mesothelioma (TTF1-)
  • Pulmonary small cell carcinoma (TTF1+) vs. Merkel cell carcinoma (TTF1-)
Micro Images

Primary lung adenocarcinoma (TTF1+)

Lung metastasis to colon (TTF1+)

Pulmonary adenocarcinoma
metastasis (left) to
renal cell carcinoma (right)
CK7 (2A); TTF1+ (2B); RCC (2C)

Positive Staining - Normal
  • Lung type II pneumocytes and Clara cells; thyroid follicular and parafollicular C cells
Positive Staining - Disease
Negative Staining
  • Merkel cell carcinoma of skin, most non-pulmonary non-small cell carcinomas