HER2 Amp, Misc Tumor, FISH, Tissue (H2MT)

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Marshfield Clinic Public WebSite

Test Code: H2MTFSO

Overview
Ordering
Specimen
Performing
Clinical/Interpretive
Contacts
Coding

Synonyms/Keywords

c-erb-b2 Amplification Test

Colorectal adenocarcinoma

Uterine serous carcinoma

Endometrial serous carcinoma

HER2 Amplification, Miscellaneous Tumor, FISH, Tissue

TI H2MTFSO

Useful For

This test is only performed on specimens from patients with primary or metastatic tumors other than breast or gastroesophageal.

Guiding cancer therapy, 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

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	Tissue Slides		4 unstained slides, 1 H&E slide	2 unstained, 1 H&E slide

Collection Processing Instructions

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

Tissue Slides: Submit 1 slide stained with hematoxylin and eosin and four consecutive, unstained, positively charged, unbaked slides with 5 micron-thick sections of tumor tissue. Slides cut from blocks prepared with alternative fixation methods may be acceptable; provide fixation method used.

Necessary Information:

1. A pathology report is required in order for testing to be performed.

2. A reason for testing must be provided.

3.The following information must be included: patient name, block number - must be on all blocks, slides and paperwork, date of collection, tissue source. Fixation used AND time in fixation (recommended: >6 hours and < 72 hours).

Specimen Stability Information

Specimen Type	Temperature
Tissue	Ambient (preferred)
Tissue	Refrigerated

Rejection Criteria

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Interference

Optimum fixation should be between 6 and 72 hours in 10% neutral buffered formalin. Other fixation methods should not be used, but the specimen will not be rejected.

Paraffin-embedded tissues that have been decalcified may not be successful for fluorescence in situ hybridization (FISH) analysis. The success rate of FISH studies on decalcified tissue is approximately 50%, but FISH will be attempted if sufficient tumor is present for analysis.

This test is not approved by the US Food and Drug Administration, and it is best used as an adjunct to existing clinical and pathologic information.

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.

Performing Laboratory Information

Performing Location	Day(s) Test Performed	Report Available	Methodology/Instrumentation
Mayo Clinic Laboratories	Monday through Friday	6-8 days	Fluorescence In Situ Hybridization (FISH)

Reference Lab

Mayo Clinic Laboratories

Test Information

In much the same way as was demonstrated for HER2-positive breast cancer, the HER2 gene status in some cancers can be used to determine treatment approaches. Amplification of the HER2 gene and overexpression of the human epidermal growth factor receptor 2 (HER2) protein have been associated with a shorter disease-free survival and shorter overall survival in some cancers. Patients whose tumors demonstrate HER2 amplification or overexpression may be candidates for treatment with the drugs that target the HER2 protein or its downstream pathways (eg, trastuzumab [Herceptin], pertuzumab).

Reference Range Information

An interpretative report will be provided.

Interpretation

Results for tumors of colorectal origin are interpreted with reference to the definition of HER2 amplification in colorectal cancer in the HERACLES trial, a HER2 / centromere ratio 2.0 or above is considered positive(2) as well as with reference to the MyPathway trial, a HER2 / centromere ratio above 2.0 or average HER2 copy number above 6.0 is considered positive.(3)

Results for primary or metastatic endometrial serous carcinomas are interpreted according to expert recommendations(4) and according to updated American Society of Clinical Oncology/College of American Pathologists (ASCP/CAP) (2018) guidelines for breast cancer.(5)

All other tumors are interpreted as amplified if HER2 / centromere ratio is greater than or equal to 2.0 or average HER2 copy number greater than or equal to 6.0 and according to according to updated ASCO/CAP (2013) guidelines for breast cancer.(1)

The degree of HER2 amplification varies in tumors. Some exhibit a high level 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 a similar prognosis or response to therapy.

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

Outreach CPTs

CPT	Modifier (if needed)	Quantity	Description	Comments
88377		1	Each multiplex probe stain procedure