Guiding 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)
Confirming the presence of HER2 amplification in cases with 2+ (low level) or 3+ (high level) HER2 protein overexpression by immunohistochemistry, and for certain histologic subtypes with aberrant patterns of HER2 expression seen by immunohistochemistry (eg, micropapillary carcinoma).
This test does not include a pathology consult. If a pathology consult is requested, PATHC / Pathology Consultation should be ordered and the appropriate FISH test will be ordered and performed at an additional charge.
Note: in accordance to criteria set forth in the 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline for breast cancer, reflex testing will not be performed using an alternative chromosome 17 probe when the FISH result is equivocal.
A charge and CPT code is applied for each probe set hybridized, analyzed, and reported.
Fluorescence In Situ Hybridization (FISH)
Bladder Cancer
c-erb-b2 Amplification Test
Urinary Bladder (UCB)
This test does not include a pathology consult. If a pathology consult is requested, PATHC / Pathology Consultation should be ordered and the appropriate FISH test will be ordered and performed at an additional charge.
Note: in accordance to criteria set forth in the 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline for breast cancer, reflex testing will not be performed using an alternative chromosome 17 probe when the FISH result is equivocal.
A charge and CPT code is applied for each probe set hybridized, analyzed, and reported.
Tissue
This test is only for primary or metastatic urothelial tumors.
-For breast tumors, order H2BR / HER2 Amplification Associated with Breast Cancer, FISH, Tissue.
-For gastroesophageal tumors, order H2GE / HER2 Amplification Associated with Gastroesophageal Cancer, FISH, Tissue.
-For all other tumor types, order H2MT / HER2 Amplification, Miscellaneous Tumor, FISH, Tissue.
Advise Express Mail or equivalent if not on courier service.
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 of fixation used as well as the time of fixation (recommended: >6 hours and <72 hours).
| Question ID | Description | Answers |
|---|---|---|
| GC034 | Reason for Referral |
Submit only 1 of the following specimens:
Specimen Type: Tissue
Preferred: Tissue block
Collection Instructions: Submit a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block. Blocks prepared with alternative fixation methods may be acceptable; provide fixation method used.
Acceptable: Slides
Collection Instructions: Four consecutive, unstained, 5 micron-thick sections placed on positively charged slides, and 1 hematoxylin and eosin-stained slide.
If not ordering electronically, complete, print, and send a Oncology Test Request (T729) with the specimen.
Two consecutive, unstained, 5-micron-thick sections placed on positively charged slides and 1 hematoxylin and eosin-stained slide.
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Tissue | Ambient (preferred) | ||
| Refrigerated | |||
Guiding 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)
Confirming the presence of HER2 amplification in cases with 2+ (low level) or 3+ (high level) HER2 protein overexpression by immunohistochemistry, and for certain histologic subtypes with aberrant patterns of HER2 expression seen by immunohistochemistry (eg, micropapillary carcinoma).
This test does not include a pathology consult. If a pathology consult is requested, PATHC / Pathology Consultation should be ordered and the appropriate FISH test will be ordered and performed at an additional charge.
Note: in accordance to criteria set forth in the 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline for breast cancer, reflex testing will not be performed using an alternative chromosome 17 probe when the FISH result is equivocal.
A charge and CPT code is applied for each probe set hybridized, analyzed, and reported.
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.
An interpretative report will be provided.
An interpretive report will be 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 (Group 4) results as defined by 2013 ASCO/CAP guidelines will no longer have reflex testing performed using an alternative FISH probe set. The report will include a complete interpretation including the HER2:D17Z1 results.
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.
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.
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. 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
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-stained 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 a ratio of HER2: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 www.cap.org/apps/docs/committees/immunohistochemistry/validated_dual_probe_ish_assay.pdf.
(Unpublished Mayo method).
Monday through Friday
This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.
88377
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| H2UR | HER2, Urothelial Tumor, FISH,Tissue | 96893-3 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 603107 | Result Summary | 50397-9 |
| 603108 | Interpretation | 69965-2 |
| 603109 | Result | 62356-1 |
| GC034 | Reason for Referral | 42349-1 |
| 603110 | Specimen | 31208-2 |
| 603111 | Source | 85298-8 |
| 603112 | Tissue ID | 80398-1 |
| 603113 | Fixative | 8100-0 |
| 603114 | Method | 85069-3 |
| 603115 | Additional Information | 48767-8 |
| 603116 | Disclaimer | 62364-5 |
| 603117 | Released By | 18771-6 |