Test Id : H2GE

This test includes a charge for the probe application, analysis, and professional interpretation of results for one probe set (2 individual fluorescence in situ hybridization [FISH] probes). No analysis charges will be incurred if an insufficient number of representative cells are available for analysis.

Note: In accordance with criteria outlined in the 2013 American Society of Clinical Oncology/College of American Pathologists guideline for breast cancer, reflex testing will not be performed using an alternative chromosome 17 probe when the FISH result is equivocal.(1)

Appropriate ancillary probes may be performed at consultant discretion to render comprehensive assessment. Any additional probes will have the results included within the final report and will be performed at an additional charge.

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

This test is not appropriate if the specimen is derived from primary or metastatic breast carcinoma. See H2BR / HER2 Amplification Associated with Breast Cancer, FISH, Tissue. If this test is ordered and the laboratory is informed that the specimen is a primary or metastatic breast carcinoma, it will be canceled and automatically reordered by the laboratory as H2BR.

For all other tumor types, order H2MT / HER2 Amplification, Miscellaneous Tumor, FISH, Tissue. If this test is ordered and the laboratory is informed that the specimen is a primary or metastatic colorectal adenocarcinoma, endometrial serous carcinoma, urothelial carcinoma, or any other non-breast or non-gastroesophageal primary or metastatic tumor, it will be canceled and automatically reordered by the laboratory as H2MT.

This test does not include a pathology consult. If a pathology consultation is requested, order PATHC / Pathology Consultation, and the appropriate testing will be added at the discretion of the pathologist and performed at an additional charge.

Advise Express Mail or equivalent if not on courier service.

1. A pathology report is required for testing to be performed. If not provided, appropriate testing and/or interpretation may be compromised or delayed. Acceptable pathology reports include working drafts, preliminary pathology, or surgical pathology reports.

2. The following information must be included in the report provided:

-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).

3. 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.

Submit only 1 of the following specimens:

Preferred

Specimen Type: Tissue block

Collection Instructions: Submit a formalin-fixed, paraffin-embedded tumor tissue block. Blocks prepared with alternative fixation methods may be acceptable; provide fixation method used.

Acceptable

Specimen Type: Tissue slides

Slides: 1 Hematoxylin and eosin stained and 4 unstained

Collection Instructions: Submit 1 slide stained with hematoxylin and eosin and 4 consecutive, unstained, positively charged, unbaked slides with 5-micron-thick sections of the tumor tissue. Slides cut from blocks prepared with alternative fixation methods may be acceptable; provide fixation method used.

If not ordering electronically, complete, print, and send a Oncology Test Request (T729) with the specimen.

Slides: 1 Hematoxylin and eosin-stained and 2 unstained

A predictive marker for patients with both node-positive or node-negative primary and metastatic gastroesophageal cancer

Guiding therapy for patients with primary or metastatic gastroesophageal 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 or absence of HER2 amplification in cases with 2+ (equivocal) HER2 overexpression by immunohistochemistry

This test includes a charge for the probe application, analysis, and professional interpretation of results for one probe set (2 individual fluorescence in situ hybridization [FISH] probes). No analysis charges will be incurred if an insufficient number of representative cells are available for analysis.

Note: In accordance with criteria outlined in the 2013 American Society of Clinical Oncology/College of American Pathologists guideline for breast cancer, reflex testing will not be performed using an alternative chromosome 17 probe when the FISH result is equivocal.(1)

Appropriate ancillary probes may be performed at consultant discretion to render comprehensive assessment. Any additional probes will have the results included within the final report and will be performed at an additional charge.

Gastroesophageal cancer is one of the most diagnosed cancers. To date, chemotherapy for gastroesophageal cancer is often ineffective, and its prognosis remains poor. Recent studies suggest that the HER2 oncogene can be used as a marker to identify aggressive disease.

In much the same way as was demonstrated for HER2-positive breast cancer, the HER2 gene status in gastroesophageal 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 gastric and gastroesophageal junction 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).

An interpretative report will be provided.

An interpretive report will be provided. Results are interpreted utilizing the 2016 College of American Pathologists/American Society for Clinical Pathology/American Society of Clinical Oncology guidelines for gastric tumors (2) and the guidelines used by the Traztuzumab for Gastric Cancer (ToGA) trial.(3)

Specimens with equivocal results as defined by 2016 CAP/ASCP/ASCO guidelines will not have additional testing performed using an alternative fluorescence in situ hybridization 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 or response to therapy.

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.

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.

1. 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 Oncol. 2013;31(31):3997-4013

2. Bartley AN, Washington MK, Ventura CB, et al. HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology. Am J Clin Pathol. 2016;146(6):647-669

3. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomized controlled trial. Lancet. 2010;376(9742):687-697

4. Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008;52:797-805

5. Reichelt U, Duesedau P, Tsourlakis MCh, et al. Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus. Mod Pathol. 2007;20:120-129

The test is performed using the PathVysion HER2 DNA probe set (Abbott Molecular) with a HER2 probe and a chromosome 17 centromere probe (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 engraving tool on the back of the unstained slide to be assayed. The probe set 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.(Unpublished Mayo method)

Monday through Friday

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• Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
• Prospective clients should contact their account representative. For assistance, contact Customer Service.

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

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