HER2

HER2 stands for human epidermal growth factor receptor 2. It is a gene that helps control how cells grow and divide. HER2 is part of a family of proteins that act as receptors on the surface of cells, receiving signals that promote cell growth. Normally, HER2 is present in small amounts on the surface of specific cells, but in some cancers, the HER2 gene becomes amplified, leading to an overproduction of the HER2 protein. This can cause uncontrolled cell growth and lead to tumour development.

What is the normal function of HER2 in a cell?

In a healthy cell, the HER2 protein receives growth signals from the surrounding environment. When growth factors bind to the HER2 protein, it activates signalling pathways that tell the cell to grow and divide. This process is tightly regulated to ensure that cells grow only when necessary. HER2 plays an important role in maintaining normal cell functions and tissue health.

What types of cancer are associated with abnormal HER2?

Abnormal HER2 is most commonly associated with breast cancer, but it is also found in some stomach and esophageal cancers. In these cancers, the HER2 gene is amplified, meaning there are extra copies of the gene that lead to the overproduction of the HER2 protein. This overexpression drives rapid and uncontrolled cell growth, contributing to tumour development. HER2-positive cancers tend to grow more aggressively, but they can respond well to targeted therapies that block HER2 activity.

What kinds of tests do pathologists perform to look for abnormal HER2, and how will the tests be described in a pathology report?

Pathologists use two main types of tests to evaluate HER2 status in cancer cells: immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).

Immunohistochemistry (IHC)

This test looks for the amount of HER2 protein on the surface of the cancer cells. The results are scored on a scale from 0 to 3+:

• 0 or 1+: This means the cancer cells do not overexpress HER2, and the tumour is considered HER2-negative.
• 2+: This is an equivocal result, meaning the HER2 status is uncertain. In this case, further testing, typically with FISH, is needed.
• 3+: This means the cancer cells have a high level of HER2 protein, and the tumour is considered HER2-positive.

Fluorescence in situ hybridization (FISH)

This test looks for extra copies of the HER2 gene in the cancer cells. FISH results are usually described as either positive or negative:

• Positive: This means there are extra copies of the HER2 gene (gene amplification), and the tumour is considered HER2-positive.
• Negative: This means there is no amplification of the HER2 gene, and the tumour is considered HER2-negative.

In your pathology report, if IHC is performed first and the result is 0, 1+, or 3+, the report usually indicates that no further testing is necessary. If the IHC result is 2+ (equivocal), FISH testing will be done to clarify the HER2 status. If both tests are conducted, the report will provide both the IHC score and the FISH result.

These tests are critical for determining treatment options, as HER2-positive cancers can be treated with drugs that specifically target the HER2 protein, such as trastuzumab (Herceptin), which can improve outcomes for patients with HER2-positive tumours.

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