HER2 Status - Histology

What is HER2?

HER2, also known as human epidermal growth factor receptor 2, is a protein encoded by the ERBB2 gene. It plays a crucial role in the growth, division, and repair of cells. In histology, HER2 is particularly significant in the context of breast cancer.

Why is HER2 Status Important?

The status of HER2 is a critical factor in determining the appropriate treatment for breast cancer patients. HER2-positive cancers tend to grow more rapidly and are more likely to spread than HER2-negative cancers. Therefore, knowing the HER2 status can help guide targeted therapy options.

How is HER2 Status Determined?

HER2 status can be determined using various histological techniques:

1. Immunohistochemistry (IHC): This method involves staining the tissue sample with antibodies that bind to the HER2 protein. The intensity of the staining is then evaluated to determine the HER2 status (scored as 0, 1+, 2+, or 3+).

2. Fluorescence In Situ Hybridization (FISH): This technique detects HER2 gene amplification by labeling DNA probes with fluorescent markers. It is used when IHC results are ambiguous (2+).

3. Chromogenic In Situ Hybridization (CISH) and Silver-enhanced In Situ Hybridization (SISH): These are alternative methods similar to FISH but use chromogenic or silver-based detection instead of fluorescence.

Interpretation of HER2 Test Results

- HER2-Positive: If the IHC score is 3+ or if FISH/CISH/SISH shows gene amplification, the cancer is considered HER2-positive. This means that the cancer cells have more HER2 receptors than normal.
- HER2-Negative: If the IHC score is 0 or 1+, or FISH/CISH/SISH shows no gene amplification, the cancer is HER2-negative.
- Equivocal: An IHC score of 2+ is considered equivocal, necessitating further testing with FISH, CISH, or SISH to confirm the HER2 status.

Clinical Implications of HER2 Status

HER2 status has significant implications for the treatment and prognosis of breast cancer:

- Targeted Therapy: HER2-positive patients can benefit from targeted therapies like trastuzumab (Herceptin) and pertuzumab (Perjeta), which specifically target HER2 receptors.
- Prognosis: HER2-positive breast cancers generally have a worse prognosis compared to HER2-negative cancers. However, targeted therapies have significantly improved outcomes for these patients.

Challenges and Limitations

Despite the advancements, there are some challenges and limitations in determining HER2 status:

- Interobserver Variability: Interpretation of IHC results can be subjective, leading to variability between different pathologists.
- Technical Issues: Both IHC and FISH require high-quality tissue samples and precise technical execution.
- Cost and Accessibility: Advanced techniques like FISH can be costly and may not be readily available in all clinical settings.

Conclusion

HER2 status is a pivotal factor in the diagnosis, treatment, and prognosis of breast cancer. Histological techniques like IHC and FISH are essential for accurately determining HER2 status, guiding the use of targeted therapies. Despite certain challenges, advancements in histology continue to improve the precision and reliability of HER2 testing, ultimately enhancing patient care.