HER2

HER2 stands for “human epidermal growth factor receptor 2.” It is a gene that provides instructions for making a protein found on the surface of specific cells. Normally, this protein helps control how cells grow, divide, and repair themselves. However, in some cancers, the cells have too many copies of the gene, resulting in the overproduction of the HER2 protein. When this occurs, cells grow and multiply uncontrollably, resulting in the growth of cancer.

What does HER2 normally do in cells?

In healthy cells, HER2 proteins act like receptors or “receiving antennas” on the cell surface. They catch growth signals from the surrounding environment, which trigger the cell to grow and divide. This process is carefully regulated, ensuring that cells only grow when necessary, which helps maintain healthy tissue.

HER2-positive cancer

Abnormal HER2 expression—often called HER2-positive status—is most commonly seen in breast cancer. However, it can also occur in other cancers, including stomach cancer (gastric cancer), esophageal cancer, ovarian cancer, uterine (endometrial) cancer, lung cancer, bladder cancer, colon cancer, and salivary gland cancer. In these cancers, having too many copies of the HER2 gene (gene amplification) leads to the overproduction (overexpression) of the HER2 protein. HER2-positive cancers typically grow faster and may spread more aggressively, but they often respond well to targeted therapies designed to block the HER2 protein.

Testing for HER2

Pathologists commonly use two tests to determine HER2 status in cancer cells: immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).

Immunohistochemistry (IHC)

Immunohistochemistry (IHC) measures the amount of HER2 protein present on cancer cells. The results are reported using a scoring system from 0 to 3+:

• 0 or 1+ (negative): Little or no HER2 protein is present. The cancer is considered HER2-negative.

• 2+ (equivocal): Moderate levels of HER2 protein. Results are unclear, and further testing, usually by FISH, is needed.

• 3+ (positive): High levels of HER2 protein. The cancer is HER2-positive.

Fluorescence in situ hybridization (FISH)

FISH directly checks cancer cells for extra copies of the HER2 gene. Results are reported simply as positive or negative:

• Positive: Cancer cells have extra copies of the HER2 gene. The tumor is HER2-positive.
• Negative: No extra HER2 gene copies are found. The tumor is HER2-negative.

If the initial IHC test score is 0, 1+, or 3+, usually no further testing is required. If the score is 2+ (equivocal), FISH is performed to clarify whether the cancer is truly HER2-positive or negative. Your pathology report will indicate these results, as well as whether further testing is necessary.

Why is testing for HER2 important?

Determining HER2 status is essential for guiding cancer treatment. HER2-positive cancers can be effectively treated with specialized drugs, known as targeted therapies, that specifically block HER2 activity. Examples include trastuzumab (Herceptin) and pertuzumab, which significantly improve outcomes for patients with HER2-positive tumors.