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

HER2 Amp, Breast Cancer, FISH, Tissue (H2BR)
Test Code: HER2FSO
Synonyms/Keywords

​Breast Carcinoma

c-erb-b2 Amplification Test (FISH)

Test Components

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.

Useful For

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)​

Specimen Requirements
Fasting Required Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
​No ​Tissue ​Tissue Block
​No ​Slides ​4un, 1 H&E ​2un, 1 H&E
Collection Processing Instructions

​Submit a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block. Blocks prepared with alternative fixation methods may be acceptable; provide fixation method used.

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)

Specimen Stability Information
Specimen Type Temperature
​Tissue ​ ​Ambient (preferred)
​Refrigerated
Performing Laboratory Information
Performing Location Day(s) Test Performed Analytical Time Methodology/Instrumentation
​Mayo Clinic Laboratories ​Monday through Sunday ​6 days ​Fluorescence In Situ Hybridization (FISH)
Reference Lab
Test Information
​Mayo tests HERBN - HER Breast IHC Automated NO Reflex and/or HERBM HER Breast Semi Quant IHC Manual may be reflexed from initial testing at added cost.  HERBN test will be added automatically when appropriate.
Reference Range Information
An interpretive report will be provided. 
Interpretation

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. 

ASCO/CAP Result Category

HER2:D17Z1 ratio;

average HER2 copies per cell

Reporting approach per 2018 ASCO/CAP guidelines
Group 1HER2:D17Z1=2.00; HER2/cell  > or =4.0Positive
Group 2HER2:D17Z1=2.00; HER2/cell <4.0Reflex IHC; FISH re-analysis if 2+
Group 3HER2:D17Z1<2.00; HER2/cell > or =6.0Reflex IHC; FISH re-analysis if 2+
Group 4HER2:D17Z1<2.00; HER2/cell > or =4.0 <6.0Reflex IHC; FISH re-analysis if 2+
Group 5HER2:D17Z1<2.00; HER2/cell <4.0Negative

 

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.

Outreach CPTs
CPT Modifier
(if needed)
Quantity Description Comments
​88377 ​1
88361 ​1 ​HER Breast IHC Automated No Reflex ​if appropriate
88360 ​1 ​HER Breast Semi Quant IHC Manual ​if appropriate
Synonyms/Keywords

​Breast Carcinoma

c-erb-b2 Amplification Test (FISH)

Test Components

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.

Ordering Applications
Ordering Application Description
​Centricity ​HER2 Amp, Breast Cancer, FISH, Tissue (HER2F)
​Cerner ​HER2 Amp, Breast Cancer, FISH, Tissue (HER2F)
​COM ​HER2 Amp, Breast Cancer, FISH, Tissue (HER2F)
If the ordering application you are looking for is not listed, contact your local laboratory for assistance.
Specimen Requirements
Fasting Required Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
​No ​Tissue ​Tissue Block
​No ​Slides ​4un, 1 H&E ​2un, 1 H&E
Collection Processing

​Submit a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block. Blocks prepared with alternative fixation methods may be acceptable; provide fixation method used.

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)

Specimen Stability Information
Specimen Type Temperature
​Tissue ​ ​Ambient (preferred)
​Refrigerated
Useful For

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)​

Test Components

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.

Reference Range Information
An interpretive report will be provided. 
Interpretation

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. 

ASCO/CAP Result Category

HER2:D17Z1 ratio;

average HER2 copies per cell

Reporting approach per 2018 ASCO/CAP guidelines
Group 1HER2:D17Z1=2.00; HER2/cell  > or =4.0Positive
Group 2HER2:D17Z1=2.00; HER2/cell <4.0Reflex IHC; FISH re-analysis if 2+
Group 3HER2:D17Z1<2.00; HER2/cell > or =6.0Reflex IHC; FISH re-analysis if 2+
Group 4HER2:D17Z1<2.00; HER2/cell > or =4.0 <6.0Reflex IHC; FISH re-analysis if 2+
Group 5HER2:D17Z1<2.00; HER2/cell <4.0Negative

 

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.

For more information visit:
Performing Laboratory Information
Performing Location Day(s) Test Performed Analytical Time Methodology/Instrumentation
​Mayo Clinic Laboratories ​Monday through Sunday ​6 days ​Fluorescence In Situ Hybridization (FISH)
Reference Lab
For billing questions, see Contacts
Outreach CPTs
CPT Modifier
(if needed)
Quantity Description Comments
​88377 ​1
88361 ​1 ​HER Breast IHC Automated No Reflex ​if appropriate
88360 ​1 ​HER Breast Semi Quant IHC Manual ​if appropriate
For most current information refer to the Marshfield Laboratory online reference manual.