TTF-1 stands for thyroid transcription factor-1. It is a protein that helps the lungs and thyroid gland develop and work normally. Pathologists test for TTF-1 to learn whether a tumor started in the lung or the thyroid.
This article explains what TTF-1 is, which cells and tumors make it, how pathologists test for it, and what your report may say.
What is TTF-1?
TTF-1 is a transcription factor. A transcription factor is a protein that switches other genes on or off. TTF-1 lives in the nucleus, the part of the cell that holds its DNA. A gene named NKX2-1 makes TTF-1, so some reports use that name instead.
TTF-1 controls genes that the thyroid and lungs need. It also helps control genes in part of the developing brain.
Which normal cells make TTF-1?
In adults, only a few types of normal cells make TTF-1. They include:
- Thyroid follicular cells. These cells make thyroid hormone and thyroglobulin.
- Thyroid C cells. These cells make the hormone calcitonin.
- Type II pneumocytes. These lung cells make surfactant, a substance that keeps the air sacs open.
- Club cells. These cells line the small airways of the lung. Older reports may call them Clara cells.
Which tumors make TTF-1?
Tumors that start in the lung or thyroid often keep making TTF-1. The share of positive tumors varies by type:
Which tumors are usually TTF-1 negative?
Many tumors do not make TTF-1. A negative result can help rule out a lung or thyroid origin. Usually negative tumors include:
- Lung squamous cell carcinoma. Most lung squamous cell carcinomas are negative. Pathologists often pair TTF-1 with p40, which is positive in most squamous cell carcinomas.
- Mucinous adenocarcinoma of the lung. Mucinous adenocarcinoma is often negative, even though it starts in the lung.
- Anaplastic thyroid carcinoma. Most anaplastic thyroid carcinomas are negative.
- Mesothelioma. This tumor of the lining around the lung is negative.
- Most cancers from other organs. Adenocarcinomas from outside the lung and thyroid are rarely positive.
How do pathologists use TTF-1?
Pathologists test for TTF-1 with immunohistochemistry. This test uses an antibody that sticks to the protein. Positive cells show brown staining in the nucleus. Pathologists use TTF-1 to answer several questions:
- Where did a metastasis start? When cancer appears in a new site, a positive TTF-1 result points to the lung or thyroid. See metastasis.
- Is a lung cancer an adenocarcinoma or a squamous cell carcinoma? TTF-1 and p40 together help classify non-small cell carcinoma in a small biopsy.
- Is a tumor in the chest lining lung cancer or mesothelioma? Lung adenocarcinoma is usually positive, and mesothelioma is negative.
- Is a small cell carcinoma from the lung or the skin? Small cell carcinoma of the lung is usually positive. Merkel cell carcinoma of the skin is negative.
To tell lung from thyroid, pathologists add other stains, such as thyroglobulin. Thyroid tumors make thyroglobulin, and lung tumors do not.
What might my report say about TTF-1?
Reports describe TTF-1 results in a few standard ways. Each laboratory phrases them a little differently:
- Positive. The tumor cells make TTF-1. This supports a lung or thyroid origin.
- Negative. The tumor cells do not make TTF-1. This does not rule out lung cancer, because some lung cancers are negative.
- Focal or diffuse. Focal means only some cells stained. Diffuse means most cells stained.
- The antibody clone. Some reports name the antibody, such as 8G7G3/1 or SPT24. Different antibodies give slightly different results.
- Part of a panel. TTF-1 usually appears with other stains. The pathologist reads the pattern of all the results together.
Questions to ask your doctor
- Was my tumor tested for TTF-1?
- Was the result positive or negative?
- What does the result say about where my cancer started?
- Which other stains did the pathologist use?
- Is my lung cancer an adenocarcinoma or a squamous cell carcinoma?
- Will my tumor have molecular testing as well?
- How do these results affect my treatment?
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