26079 HER2 Amp, Breast Cancer, FISH, Tissue (H2BR)

​Breast Carcinoma

c-erb-b2 Amplification Test (FISH)

TI HER2FSO

Reflex testing will be performed using immunohistochemistry (IHC) when the FISH result falls within certain ranges as defined by the 2018 focused update to the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.(1) For FISH results in ASCO/CAP categories Group 2, 3, and 4 (formerly called "equivocal"), the IHC testing will be added, charged, and reported separately. An integrated interpretation of the IHC and FISH results will be provided (see Interpretation).

A charge and CPT code is applied for each probe set hybridized, analyzed, and reported.

​Submit a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block.

OR

Four consecutive, unstained, 5 micron-thick sections placed on positively charged slides, and 1 hematoxylin and eosin-stained slide.

1. A pathology report is required in order for testing to be performed. Acceptable pathology reports include working drafts, preliminary pathology or surgical pathology reports.

2. A reason for testing must be provided. If this information is not provided, an appropriate indication for testing may be entered by Mayo Clinic Laboratories.

3. The pathology report must include type and time of fixation, as well as the cold ischemia time.

Note: In accordance to CAP guidelines, place specimens for HER2 (ERBB2) testing in fixative within one hour of biopsy or resection (cold ischemia time). Specimens should remain in 10% neutral buffered formalin for a minimum of six hours to a maximum of 72 hours (formalin fixation time). Do not use decalcification solutions with strong acids.(2)

​Optimum fixation should be between 6 and 72 hours in 10% neutral buffered formalin. Other types of fixatives should not be used.

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, estrogen/progesterone receptor status) may be of equal or greater importance in determining the patient's prognosis.

A predictive marker for patients with both node-positive or node-negative primary and metastatic breast cancer

Patients with HER2 amplification that may be candidates for therapies targeting 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 overexpression by immunohistochemistry, and for certain histologic subtypes with aberrant patterns of HER2 expression seen by immunohistochemistry (eg, micropapillary carcinoma)​

Reflex testing will be performed using immunohistochemistry (IHC) when the FISH result falls within certain ranges as defined by the 2018 focused update to the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.(1) For FISH results in ASCO/CAP categories Group 2, 3, and 4 (formerly called "equivocal"), the IHC testing will be added, charged, and reported separately. An integrated interpretation of the IHC and FISH results will be provided (see Interpretation).

A charge and CPT code is applied for each probe set hybridized, analyzed, and reported.

An interpretive report will be provided. Results are interpreted utilizing the current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.(1) 

Under the 2018 Focused Update to the ASCO/CAP Guidelines, reflex immunohistochemistry (IHC) is performed for certain categories of results, known as Groups 2, 3, and 4. These categories are shown in the table below (Group 4 is the category formerly referred to as FISH "equivocal"). If reflex IHC is performed and is either negative (0, 1+) or positive (3+), the result of the FISH assay is considered resolved by IHC as either negative or positive. If the IHC assay shows an equivocal (2+) result, then the FISH slide is re-scored within the areas showing the most intense membranous (2+) staining and the final FISH result is used to determine whether the result is negative or positive. 

The degree of HER2 amplification varies in tumors. Some exhibit high levels of amplification (HER2:D17Z1 ratio >4.0), whereas others exhibit low-level amplification (HER2:D17Z1 ratio of 2.0-4.0). It is not currently known if patients with different levels of amplification have the same prognosis and response to therapy.

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

Rare cases may not show HER2 amplification but still 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 be candidates for treatments that target the HER2 protein or its downstream pathways.