HER2 Amplification Associated with Urothelial Carcinoma, FISH, Tissue
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
To guide therapy for patients with primary or metastatic urothelial tumors, 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
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
This test does not include a pathology consult. If a pathology consult is requested, 70012 / Pathology Consultation should be ordered and the appropriate FISH test will be ordered and performed at an additional charge.
Fluorescence In Situ Hybridization (FISH)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
HER2 Amp, Urothelial, FISH
c-erb-b2 Amplification Test
Urinary Bladder (UCB)
Urinary Bladder (UCB)
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.
Provide a pathology report with each tissue specimen. The pathology report must include type of fixation used (ie, >6 hours and <72 hours). The laboratory will not reject a specimen that arrives without this information but will hold analysis of the specimen until a pathology report is received.
Forms: If not ordering electronically, submit a Cytogenetics Hematologic Disorders Request Form (Supply T607) with the specimen.
Submit only 1 of the following specimens:
Specimen Type: Tissue
Container/Tube: Formalin-fixed, paraffin-embedded tumor tissue block
Specimen Type: Slides
Specimen Volume: 4 Consecutive, unstained, 5 micron-thick sections placed on positively charged slides and 1 hematoxylin and eosin-stained slide
Note: No specimen should be rejected. If specimen not received at appropriate temperature, include note to laboratory. If questions, contact laboratory.
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
Human epidermal growth factor receptor 2 (HER2) plays a fundamental role in cell growth, survival, and migration. The assessment of HER2 gene status is crucial for the management of breast cancer. Studies have shown that HER2 is also expressed in a proportion of urothelial carcinoma of the urinary bladder (UCB), making it a potential target for UCB therapy.
HER2-positive gene status is associated with aggressive UCB and provides independent prognostic information. Assessment of HER2 status may be used to identify patients at high risk of disease progression.
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.
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 require reflex or repeat testing per ASCO/CAP guidelines.
The degree of HER2 amplification varies in tumors. Some exhibit high levels 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 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 changes 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.
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 urothelial tumors.
-For breast tumors, order FHER2 / HER2 Amplification Associated with Breast Cancer, FISH, Tissue.
-For gastroesophageal tumors, order FH2GE / HER2 Amplification Associated with Gastroesophageal Cancer, FISH, Tissue.
-For all other tumor types, order FH2MT / HER2 Amplification, Miscellaneous Tumor, FISH, Tissue.
The HER2 FISH test is not approved by the FDA for this indication and should be used as an adjunct to existing clinical and pathologic information.
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) may be of equal or greater importance in determining the patient's prognosis.
Urothelial carcinoma samples (170) were analyzed using the PathVysion HER2 probe set and 18 (10.6%) showed HER2 amplification. These results are consistent with a published report describing 93/1005 (9.2%) samples from bladder cancer patients with HER2 amplification.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Bolenz C, Shariat SF, Karakiewicz PI, et al: Human epidermal growth factor receptor 2 expression status provides independent prognostic information in patients with urothelial carcinoma of the urinary bladder. BJU Int 2010 Oct;106(8):1216-1222
2. Lae M, Couturier J, Oudard S, et al: Assessing HER2 gene amplification as a potential target for therapy in invasive urothelial bladder cancer with a standardized methodology: results in 1005 patients. Ann Oncol 2010 Apr;21(4):815-819
3. Gandour-Edwards R, Lara PN Jr, Folkins AK, et al: Does HER2/neu expression provide prognostic information in patients with advanced urothelial carcinoma? Cancer 2002 Sep 1;95(5):1009-1015
4. 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
Method Description Describes how the test is performed and provides a method-specific reference
The test is performed using the dual-color PathVysion HER2 DNA probe set (Abbott Molecular) with a HER2 probe and a chromosome 17 centromere probe (CEP17; D17Z1). Paraffin-embedded tissues are cut at 5 microns and mounted on positively charged glass slides. The selection of tissue and the identification of target areas on the hematoxylin and eosin (H and E)-stained slide are performed by a pathologist. Using the H and E slide as a reference, target areas are etched with a diamond-tipped etcher on the back of the unstained slide to be assayed. The probe is hybridized to the appropriate target areas and 2 technologists each analyze 30 interphase nuclei (60 total) with the results expressed as the average ratio of HER2 signals as compared to D17Z1 signals. The results are interpreted based on the 2013 guidelines established by the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP), available at http://www.cap.org/apps/docs/committees/immunohistochemistry/validated_dual_probe_ish_assay.pdf.
(Unpublished Mayo method)
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; 6 a.m.-9 p.m.
Saturday, Sunday; 6 a.m.-4 p.m.
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
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 modified from the manufacturer’s instructions. Its performance characteristics were determined 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.
88271 x 2-Molecular cytogenetics (eg, FISH), each probe
88274-Interphase in situ hybridization
88291-Cytogenetics and molecular cytogenetics, interpretation and report
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|
|CG644||Reason For Referral||42349-1|