Interpretive Handbook

Test 60655 :
HER2 Amplification, Miscellaneous Tumor, FISH, Tissue

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Amplification of the HER2 oncogene and overexpression of the human epidermal growth factor receptor 2 (HER2) protein have been associated with a shorter disease-free survival and shorter overall survival and poorer overall survival in some cancers. Patients whose breast or gastroesophageal cancers demonstrate HER2 amplification or overexpression may be candidates for treatment with the drugs that target the HER2 protein or its downstream pathways (eg, trastuzumab [Herceptin], pertuzumab, lapatinib).

Useful For Suggests clinical disorders or settings where the test may be helpful

Guiding cancer therapy, as patients with HER2 amplification may be candidates for therapies that target the human epidermal growth factor receptor 2 (HER2) protein (eg, trastuzumab [Herceptin], pertuzumab, lapatinib)


Confirming the presence of HER2 amplification in cases with 2+ (low level) or 3+ (high level) HER2 protein overexpression by immunohistochemistry

Interpretation Provides information to assist in interpretation of the test results

An interpretive report is provided. Results are interpreted utilizing the 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for breast tumors.


Specimens with equivocal results as defined by 2013 ASCO/CAP guidelines will have reflex testing performed using the HER2/D17S122 probe. The report will include a complete interpretation including the HER2:D17Z1 and HER2:D17S122 results.


The degree of HER2 amplification varies in tumors. Some exhibit a high level of amplification (HER2:CEP17 ratio >4.0), whereas others exhibit low-level amplification (HER2:CEP17 ratio of 2.2-4.0). It is not currently known if patients with different levels of amplification have a similar prognosis or response to therapy.


Reports also interpret the HER2 copy number changes relative to chromosome 17 copy number (aneusomy) or potential structural changes that increase HER2 copy number.


Rare cases may not show HER2 amplification but have human epidermal growth factor receptor 2 (HER2) protein overexpression demonstrated by immunohistochemistry. The clinical significance of HER2 protein overexpression in the absence of HER2 gene amplification is unclear. However, these patients may have a worse prognosis and may be candidates for treatments that target the HER2 protein or its downstream pathways.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test is only for primary or metastatic tumors other than breast, urothelial, or gastroesophageal.

-For breast tumors, order FHER2 / HER2 Amplification Associated with Breast Cancer, FISH, Tissue.

-For urothelial tumors, order FH2UR / HER2 Amplification Associated with Urothelial Carcinoma, FISH, Tissue.

-For gastroesophageal tumors, order FH2GE / HER2 Amplification Associated with Gastroesophageal Cancer, FISH, Tissue.


This test is not approved by the FDA and should be used as an adjunct to existing clinical and pathologic information.


The prognostic information provided by the HER2 status of a patient's tumor should not be interpreted in isolation because other prognostic features (eg, lymph node status, tumor size) may be of equal or greater importance in determining the patient's prognosis.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretative report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

Wolff AC, Hammond ME, Hicks DG, et al: Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society for Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Onc 2013 Nov 1;31(31):3997-4013