HER2, Breast, Quantitative Immunohistochemistry, Automated
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Determining overexpression of HER2 protein on formalin-fixed, paraffin-embedded tissue sections
This FDA-approved test is most frequently used to evaluate HER2 overexpression in breast cancer.
Reflex Tests Lists test(s) that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial test(s)
|Test ID||Reporting Name||Available Separately||Always Performed|
|FHER2||HER2 Amp, Breast Cancer, FISH||Yes||No|
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
Cases that are equivocal (2+) by immunohistochemical stain will reflex to HER2 FISH at an additional charge.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
US Food and Drug Administration (FDA)-Approved Ventana Pathway Immunoperoxidase Stain
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
HER2, Breast IHC, Automated
c-neu Immunoperoxidase Stain
c-erbB2 Immunoperoxidase Stain
c-erbB2 Immunoperoxidase Stain
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Preferred: A paraffin-embedded tissue block containing breast cancer tissue that has been fixed in 10% neutral buffered formalin within 1 hour from surgical collection time and for a total of 6 to 48 hours and shipped at ambient temperature
Acceptable: 2 unstained sections, containing breast carcinoma, on charged slides cut at 4 microns <1 month ago and shipped at ambient temperature. Tissue on the slides should have been fixed in 10% neutral buffered formalin within 1 hour from surgical collection time and for a total of 6 to 48 hours.
Container/Tube: Surgical Pathology Packaging Kit (Supply T554)
1. Submit paraffin-embedded invasive or metastatic breast carcinoma tissue.
2. Include accompanying pathology report stating the final diagnosis. If not available, a preliminary diagnosis is acceptable only if it refers to invasive or metastatic breast carcinoma.
3. Attach the green pathology address label included in the kit to the outside of the transport container.
1. Information regarding duration of fixation is required. When ordering this test, the following questions, are stated on the order form or presented electronically, and must be answered:
-"Was specimen fixed in 10% neutral buffered formalin within 1 hour from surgical collection time? Yes, No, or Unknown."
-"Has specimen been fixed in 10% neutral-buffered formalin for 6 to 48 hours? Yes, No, or Unknown."
2. According to the College of American Pathologists (CAP)/American Society of Clinical Oncology (ASCO) guidelines, HER2 protein immunohistochemical test results are only valid for nondecalcified, paraffin-embedded specimens fixed in 10% neutral buffered formalin within 1 hour from surgical collection time and for a total time of 6 to 48 hours. Under- or overfixation may affect these results.
3. Paraffin blocks will be returned with final report.
Forms: If not ordering electronically, submit a Pathology/Cytology Request Form (Supply T246) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
The HER2 (official gene name ERBB2) proto-oncogene encodes a membrane receptor with tyrosine kinase activity and homology to the epidermal growth factor receptor.
Amplification and overexpression of the HER2 gene in human breast, endometrial, ovarian, and other epithelial cancers have been associated with a shorter disease-free interval and shorter overall survival. Overexpression of HER2 protein is an indication for Herceptin therapy in patients with breast cancer.
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.
Reported as negative (0, 1+), equivocal (2+), and strongly positive (3+) according to the interpretation guidelines for the FDA-approved Ventana Pathway HER2 (4B5) antibody.
Results are reported as negative (0, 1+), equivocal (2+), and strongly positive (3+) according to the interpretation guidelines for the FDA-approved Ventana Pathway HER2 (4B5) antibody.
The scoring method using the Aperio digital pathology system was developed and validated in the Molecular Anatomic Pathology Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic (see Method Description).
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The performance and quality of immunohistochemical stains in formalin-fixed, paraffin-embedded tissue depends critically on proper fixation.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Riber-Hansen R, Vainer B, Steiniche T: Digital image analysis: a review of reproducibility, stability and basic requirements for optimal results. Apmis 2012 April;120(4):276-289
2. Gavrielides MA, Gallas BD, Lenz P, et al: Observer variability in the interpretation of HER2/neu immunohistochemical expression with unaided and computer-aided digital microscopy. Arch Pathol Lab Med Feb;135(2):233-242
3. Cuadros M, Villegas R: Systematic review of HER2 breast cancer testing. Appl Immunohistochem Mol Morphol Jan 2009;17(1):1-7
4. Nassar A, Cohen C, Agersborg SS, et al: Trainable immunohistochemical HER2/neu image analysis: a multisite performance study using 260 breast tissue specimens. Arch Pathol Lab Med 2011 July;135(7):896-902
5. Wolff AC, Hammond ME, Schwartz JN, et al: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med 2007;131:18-43
Method Description Describes how the test is performed and provides a method-specific reference
Testing is performed using FDA-approved Ventana Pathway HER2 (4B5) rabbit monoclonal primary antibody and a proprietary detection system.(Package insert: PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody)
No expression (HER2 score of 0), low expression (HER2 score of 1+) and high expression (HER2 score of 3+) controls are used. HER2 immunohistochemical (IHC) slides are scanned using the Aperio ScanScope instrument, which captures digital images of the patient slide. The technologist views the digitized image on a computer monitor and using a tracing tool available in ImageScope (Aperio Technologies Inc), traces around areas of invasive cancer capturing no less than 75% of the total cancer within the image. The traced areas are then analyzed using a laboratory-developed image analysis algorithm designed to maximize concordance with HER2 fluorescence in situ hybridization. All analyzed cells are identified as having either a HER2 staining intensity of 0, 1+, 2+, or 3+. A case will be called 3+ if 30% or more of the cells fall into the 3+ category, which is in accordance with CAP/ASCO guidelines. Cases will be called 2+ if more than 10% of the cells are stained at the 2+ level, 1+ if more than 10% are stained at the 1+ level, and 0 if less than 10% of the cells are stained at the 1+ or higher levels. In cases with less than 30% of cells staining at the 3+ level, the highest score (2+, 1+, or 0) that has at least 10% of cells staining at that level will be the final score. The slides and test results are then reviewed by a pathologist who provides a final interpretation.(Wolff AC, Hammond ME, Schwartz JN, et al: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med 2007;131:18-43)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Friday
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Until 1 week after results are reported
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test has been cleared or approved by the U.S. Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
HER2, Breast, Quantitative Immunohistochemistry, Automated
88361-Morphometric analysis (eg, Her-2/neu, estrogen/progesterone receptor), tumor-immunohistochemistry, quantitative or semiquantitative, each antibody; using computer-assisted technology
HER2 Amplification Associated with Breast Cancer, FISH, Tissue
88271 x 2-Molecular cytogenetics (eg, FISH), each probe (if appropriate)
88274-Interphase in situ hybridization (if appropriate)
88291-Cytogenetics and molecular cytogenetics, interpretation and report (if appropriate)
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|18932||Ref Path/Phys Address||In Process|
|18935||SP Signing Pathologist:||N/A|
|18936||*Previous Report Follows*||N/A|