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Stains

TTF1

Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 22 November 2012, last major update April 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.

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


Primary lung adenocarcinoma (TTF1+)


Lung metastasis to colon (TTF1+)

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

End of Stains > TTF1

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