HER2 Immunohistochemistry (IHC) is a diagnostic test frequently employed in cancer care, particularly for breast and gastric cancers. It helps determine the presence and quantity of the Human Epidermal growth factor Receptor 2 (HER2) protein on cancer cells. Understanding a tumor’s HER2 status provides valuable information, directly influencing treatment strategies. These insights guide oncologists in tailoring therapies to a patient’s specific cancer characteristics.
What is HER2 and Why is it Tested?
HER2 (Human Epidermal growth factor Receptor 2) is a protein on the surface of cells throughout the body. It belongs to a family of receptors that regulate cell growth, division, and repair. In healthy cells, HER2 proteins are present in normal amounts, ensuring controlled cellular processes.
In some cancers, particularly breast and gastric cancers, cells produce an abnormally high number of HER2 proteins, known as overexpression. This overexpression is often due to an increased number of HER2 gene copies (gene amplification) within cancer cells. When too many HER2 proteins are present, they send excessive signals, leading to uncontrolled cell growth and division, contributing to more aggressive tumor behavior and a higher risk of recurrence.
HER2 testing provides two key pieces of information. First, it offers prognostic insight, as tumors with HER2 overexpression tend to grow and spread more quickly. Second, it guides treatment decisions. It identifies patients whose cancers may respond to specific targeted therapies designed to block HER2 protein activity. These treatments are ineffective for cancers that do not overexpress HER2.
The Immunohistochemistry Process
HER2 testing begins with a tissue sample, usually from a biopsy or surgery. The tissue is processed in a laboratory to preserve its cellular structure and proteins. The sample is embedded in paraffin wax, cut into thin sections, and placed onto glass slides.
Immunohistochemistry uses specific antibodies. Technicians apply antibodies designed to bind to the HER2 protein in the tissue sample. These antibodies are linked to a detectable marker, often an enzyme that produces a colored reaction when exposed to a substrate. This colored product allows a pathologist to visualize and assess the amount and pattern of HER2 protein on cancer cells under a microscope.
Interpreting HER2 IHC Results
Pathologists interpret HER2 IHC results using a standardized scoring system, which categorizes the level of HER2 protein expression from 0 to 3+. Scoring is based on the intensity and completeness of membrane staining on cancer cells.
A score of 0 indicates no membrane staining or faint staining in 10% or fewer tumor cells, classifying the cancer as HER2-negative. A 1+ score means faint or incomplete membrane staining in more than 10% of tumor cells, also considered HER2-negative. Cancers with these scores do not benefit from HER2-targeted therapies.
A 3+ score signifies strong, complete membrane staining in more than 10% of invasive tumor cells. This indicates high HER2 protein overexpression, classifying the cancer as HER2-positive. These tumors are likely to respond to HER2-targeted treatments.
A 2+ score is considered equivocal or borderline. This indicates weak to moderate complete membrane staining in more than 10% of tumor cells, but the HER2 protein level is not definitively positive by IHC alone. Further testing is necessary to confirm HER2 status. This often involves techniques like Fluorescence In Situ Hybridization (FISH) or Chromogenic In Situ Hybridization (CISH), which assess HER2 gene copies rather than just the protein.
HER2 Status and Treatment Decisions
The HER2 status of a cancer directly impacts the treatment approach, particularly for breast and gastric cancers. If a cancer is confirmed HER2-positive, either by an IHC score of 3+ or by follow-up FISH/CISH testing for equivocal (2+) cases, patients become candidates for specific HER2-targeted therapies. These medications are designed to interfere with the HER2 protein, thereby inhibiting cancer cell growth and improving patient outcomes.
Examples of HER2-targeted therapies include monoclonal antibodies like trastuzumab and pertuzumab, which attach to the HER2 protein on the cancer cell surface to block its signaling. Ado-trastuzumab emtansine, an antibody-drug conjugate, delivers chemotherapy directly to HER2-positive cells. Neratinib, a kinase inhibitor, also blocks HER2 activity. These treatments are often administered in combination with chemotherapy, and for early-stage HER2-positive breast cancer, they can significantly reduce the risk of recurrence.
For cancers classified as HER2-negative (IHC 0 or 1+, or negative by FISH/CISH), HER2-targeted therapies are not effective because these cells do not overexpress the HER2 protein. Treatment for HER2-negative cancers typically involves other approaches, which may include chemotherapy, hormone therapy (if the cancer is hormone receptor-positive), or immunotherapy. The specific regimen is tailored based on the cancer’s stage, grade, and other molecular characteristics. Accurate HER2 testing is therefore paramount, as it ensures patients receive treatments most likely to be beneficial while avoiding ineffective therapies that could carry unnecessary side effects.