HER2 Staining: What the Results Mean for Treatment

Human Epidermal Growth Factor Receptor 2 (HER2) is a protein on the surface of cells that regulates their growth. In some cancers, particularly certain breast cancers, cells produce an excessive amount of this protein, causing them to multiply rapidly. A HER2 staining test is a diagnostic procedure that measures the amount of this protein in cancer cells. For anyone diagnosed with an invasive breast cancer, HER2 testing is a standard part of the initial diagnosis to help guide treatment.

The HER2 Staining Procedure

Determining a tumor’s HER2 status begins with a procedure called immunohistochemistry (IHC). This lab test is performed on a small piece of tumor tissue removed during a biopsy or surgery. The tissue sample is thinly sliced so it can be examined under a microscope, ensuring the cellular structure remains intact for analysis.

To visualize the HER2 proteins, the tissue sample is treated with antibodies designed to bind exclusively to HER2 receptors on the cancer cells. This specificity allows pathologists to isolate and identify the target protein among all other cellular components.

A chemical dye linked to these antibodies makes the HER2 proteins visible when they attach. A pathologist then observes the amount and pattern of this staining under a microscope. The intensity and distribution of the color provide the basis for scoring the tumor’s HER2 status.

Scoring and Interpreting Staining Results

A pathologist scores the results based on a standardized system. The score evaluates the quantity of HER2 protein by observing the stain’s intensity and whether it forms complete rings around the cancer cell membranes.

A result of 0 or 1+ is considered HER2-negative. A score of 0 means no staining is visible, while a 1+ score signifies faint and incomplete staining on some cells. In both cases, the amount of HER2 protein is not high enough to be a factor in the cancer’s growth.

A score of 3+ is an HER2-positive result. This score is given when a pathologist observes strong, complete staining around the entire membrane of more than 10% of the tumor cells. This pattern indicates a significant overexpression of the HER2 protein, identifying it as a driver of the cancer’s growth.

A score of 2+ is classified as borderline or equivocal. This result occurs with moderate, complete staining of the cell membranes, but the intensity is not strong enough to be clearly positive. Because this ambiguity means the IHC test is insufficient, a 2+ score requires additional testing to clarify the tumor’s HER2 status.

Confirming Borderline Results

An equivocal IHC score of 2+ is ambiguous because it falls between negative and positive. To resolve this, a follow-up test is performed to examine the cancer cells at a genetic level, since the IHC test only measures protein on the cell surface.

This confirmatory test is a form of in situ hybridization (ISH), most commonly Fluorescence In Situ Hybridization (FISH). Instead of looking for proteins, the FISH test counts the number of HER2 genes inside each cancer cell. The HER2 gene contains the instructions for making the HER2 protein, so an excess number of gene copies leads to protein overexpression.

The FISH test uses fluorescent probes that attach to the HER2 gene. Viewed with a fluorescence microscope, these probes light up, allowing pathologists to count the genes in each cell. An abnormally high number of HER2 gene copies confirms a positive result. This genetic evidence resolves the ambiguity of a 2+ IHC score and establishes the tumor’s final HER2 status.

How HER2 Status Guides Cancer Treatment

A tumor’s confirmed HER2 status is a deciding factor in a patient’s treatment plan. If a tumor is HER2-positive, its growth is driven by an overabundance of HER2 proteins. This makes the cancer susceptible to a class of drugs known as targeted therapies.

These treatments are designed to attack HER2-positive cancer cells. Medications like trastuzumab and pertuzumab are antibodies that attach to the HER2 receptors on cancer cells. By blocking these receptors, the drugs interrupt growth signals, which can slow or stop the cancer from growing. They may also mark the cancer cell for destruction by the immune system.

Targeted therapies are not beneficial for HER2-negative tumors, as the cancer cells lack the protein target. For these cancers, the treatment plan will focus on other approaches, such as hormone therapy or chemotherapy. The HER2 test result therefore directly informs the selection of the most effective therapies for an individual’s cancer.

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