General
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• 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
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• 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
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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
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• Lung type II pneumocytes and Clara cells; thyroid follicular and parafollicular C cells

Positive staining - disease
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• Lung carcinoma: small cell (90%), adenocarcinoma (75%); large cell (40%); squamous cell (5%, Am J Surg Pathol 2001;25:363)
• Thyroid: hyperplastic and neoplastic thyroid tissue, but less common / lower levels in undifferentiated thyroid carcinomas (Mod Pathol 2000;13:570)
• Other tumors: small cell carcinomas of lung and various sites (Mod Pathol 2000;13:238; Am J Surg Pathol 2001;25:815); colorectal carcinomas to lung may be positive (Mod Pathol 2005;18:1371), small cell carcinoma of bladder (39%, Hum Pathol 2005;36:718)

Negative staining
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• Merkel cell carcinoma of skin, most non-pulmonary non-small cell carcinomas

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