Napsin A: Definition

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Napsin A is a protein made by certain cells in the lungs and kidneys. Pathologists test for Napsin A mainly to help diagnose lung adenocarcinoma, the most common type of lung cancer, and to separate it from other types of lung cancer. Napsin A also helps identify clear cell carcinomas of the ovary and uterus, as well as some kidney cancers.

This article explains what Napsin A is, which cells make it, how pathologists use it to diagnose cancer, and what a Napsin A result in your pathology report means.

What is Napsin A?

Napsin A is an enzyme, a type of protein that helps chemical reactions happen inside a cell. In the lungs, it helps prepare surfactant, the slippery substance that keeps the tiny air sacs from collapsing each time you breathe out. Napsin A sits in the cytoplasm of the cell, the area outside the nucleus. In normal tissue, several types of cells make Napsin A:

Pneumocytes. Type II pneumocytes, the cells that make surfactant in the air sacs of the lung, are strongly positive.
Lung macrophages. These immune cells clean up the air sacs and are also positive for Napsin A.
Kidney tubules. Some small kidney tubules that handle salt and water are positive.

How do pathologists test for Napsin A?

Pathologists test for Napsin A using immunohistochemistry, which uses antibodies to detect specific proteins in a thin slice of tissue. Cells that make Napsin A show fine brown granules in their cytoplasm under the microscope. Because normal lung macrophages are also positive, the pathologist must be careful not to mistake these cells for cancer cells.

How does Napsin A help diagnose lung cancer?

Napsin A helps diagnose lung cancer because most lung adenocarcinomas make this protein, while most other lung cancers do not. It is usually tested together with TTF-1, a related marker that controls the Napsin A gene. Typical patterns include:

Lung adenocarcinoma. The cancer cells are usually positive for both TTF-1 and Napsin A.
Squamous cell carcinoma of the lung. The cancer cells are usually negative for both markers and instead positive for squamous markers.
Small cell carcinoma. The cancer cells are often positive for TTF-1 but negative for Napsin A.

Knowing the exact type of lung cancer matters because it guides which further tests, such as biomarker tests, your doctors will order. Napsin A also helps when doctors find a cancer in another organ, such as the brain or a lymph node. A positive result suggests that the cancer may have started in the lung.

Where else do pathologists use Napsin A?

Pathologists also use Napsin A to help identify a few cancers outside the lung. In these cancers, the staining is sometimes weak or limited to a small number of cells. Examples include:

Clear cell carcinoma of the ovary and uterus. Most cases of ovarian clear cell carcinoma and many cases of endometrial clear cell carcinoma are positive, which helps separate them from other types of ovarian and uterine cancer.
Papillary renal cell carcinoma. Many cases of this kidney cancer are positive for Napsin A, while the more common clear cell type usually is not.
Papillary thyroid carcinoma. A minority of these thyroid cancers are positive, which the pathologist keeps in mind when using Napsin A to look for a lung cancer.

What does a Napsin A result mean in my report?

A Napsin A result in your report describes whether the abnormal cells make this protein. Your report may describe the result in one of a few ways:

Positive. The cancer cells make Napsin A, which supports a diagnosis of lung adenocarcinoma or another Napsin A-positive cancer when the other markers fit.
Negative. The cancer cells do not make Napsin A, which points toward a different type of cancer, although a negative result does not rule out adenocarcinoma.
Focal or weak. Only some of the cancer cells are positive, or the staining is faint, a result the pathologist interprets together with TTF-1 and other markers.

Questions to ask your doctor

Were the cancer cells in my sample positive or negative for Napsin A?
Were they also positive for TTF-1?
What type of lung cancer do I have?
Did the cancer start in my lung, or did it spread there from somewhere else?
Will my cancer need biomarker tests?
Which other markers did the pathologist use to confirm the diagnosis?