PTEN

PTEN (short for phosphatase and tensin homolog) is a gene that helps control how cells grow and divide. It is called a tumor suppressor gene because it helps prevent cells from growing out of control. The PTEN gene makes a protein that is found in most tissues in the body, where it plays a key role in keeping cell growth in check.

What does the PTEN protein do?

The PTEN protein helps regulate a system in cells called the PI3K/AKT pathway. This pathway controls how cells grow, survive, and respond to signals. PTEN slows down this pathway, preventing too much cell growth. Inside the nucleus of the cell (the part that holds the DNA), PTEN also helps keep DNA stable and helps with repair if the DNA becomes damaged.

If PTEN is missing or not functioning correctly, the PI3K/AKT pathway becomes overactive, which can lead to the development of cancer.

What types of cells normally express PTEN?

Most cells in the body produce PTEN, including cells in the colon, prostate, breast, and brain. In normal cells, PTEN is typically found in the cytoplasm (the fluid inside cells), on the cell membrane (the outer surface of the cell), and occasionally in the nucleus.

How do pathologists test for PTEN?

Pathologists most commonly test for PTEN using a method called immunohistochemistry (IHC). This test uses special antibodies that attach to the PTEN protein in a tissue sample. If the PTEN protein is present, it appears as staining that the pathologist can observe under a microscope. If the tumor cells do not show any staining, this means that PTEN has been lost or is not working correctly in those cells. Staining in nearby normal cells helps confirm that the test worked.

In some cases, pathologists may also utilize next-generation sequencing (NGS) to identify mutations or deletions within the PTEN gene itself. This is a more detailed genetic test that examines the DNA of the tumor cells. NGS can detect changes that are not visible with IHC, including subtle mutations that affect the gene’s function without completely eliminating the protein. This can be especially helpful when IHC results are unclear or when doctors need more information to guide treatment.

What types of tumors show PTEN loss?

Loss of PTEN is common in several types of cancer. These include:

• Endometrial carcinoma – PTEN is frequently lost in endometrioid carcinoma, a common type of uterine cancer.
• Prostate cancer – Over half of prostate cancers show PTEN loss. This is often linked to a higher chance of the cancer returning or spreading.
• Breast cancer – PTEN loss can occur in triple-negative breast cancers and may be linked to poorer outcomes.
• Glioblastoma – About 70% of glioblastomas, an aggressive type of brain tumor, show PTEN loss.
• Colorectal cancer – Some colorectal cancers have reduced or absent PTEN expression.
• Melanoma and pancreatic cancer – These cancers can also show PTEN loss.
• Acute myeloid leukemia (AML) – Up to 75% of AML cases show reduced or absent PTEN expression, and PTEN loss may contribute to disease progression and resistance to treatment.

What is the significance of PTEN loss in a cancer diagnosis?

The loss of PTEN may suggest that the cancer is more aggressive or likely to come back after treatment. It can also help guide treatment decisions:

• In breast cancer, patients with PTEN loss may respond differently to HER2-targeted therapies.
• In prostate cancer, PTEN loss is linked to worse outcomes and may predict resistance to specific therapies.
• In AML, PTEN loss is being studied as a factor that may influence response to treatment, including immune-based therapies.
• In endometrial cancer, PTEN loss is commonly seen and helps support the diagnosis of endometrioid carcinoma.

Can PTEN be linked to inherited conditions?

Yes. People with inherited mutations in the PTEN gene may have a condition called PTEN hamartoma tumor syndrome, which includes Cowden syndrome. These conditions increase the risk of developing noncancerous and cancerous growths in various parts of the body, including the skin, thyroid, breast, and gastrointestinal tract.

Questions to ask your doctor

• What does the PTEN result mean for my diagnosis?
• Does PTEN loss affect my treatment options?
• Is PTEN testing part of a larger panel of genetic tests for my tumor?
• Should I or my family members be tested for a genetic condition like Cowden syndrome?