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Test ID: FH2GE    
HER2 Amplification Associated with Gastroesophageal Cancer, FISH, Tissue

Useful For Suggests clinical disorders or settings where the test may be helpful

To guide therapy for patients with gastroesophageal cancer, as patients with HER2 amplification may be candidates for Herceptin therapy

 

To confirm the presence of HER2 amplification in cases with 2+ (low-level) or 3+ (high-level) HER2 protein overexpression by immunohistochemistry

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Gastroesophageal cancer is the fourth most commonly diagnosed cancer. 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 HER2 protein have been associated with a shorter disease-free survival and shorter overall survival in gastric and gastric-esophageal junction cancers. Patients whose tumors demonstrate HER2 amplification may be candidates for treatment with Herceptin (trastuzumab).

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.

Interpretation Provides information to assist in interpretation of the test results

An interpretive report is provided. Results are interpreted utilizing the 2007 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for breast tumors, and the guidelines used by the ToGA trial.(1)

 

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 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 Herceptin treatment.

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 gastroesophageal tumors. For breast tumors, order #81954 HER2 Amplification Associated with Breast Cancer, FISH, Tissue, for other tumor types, order #60655 HER2 Amplification, Miscellaneous Tumor, FISH, Tissue.

 

This indication for the HER2 FISH test is not approved by the FDA and should be used as an adjunct to existing clinical and pathologic information.

 

The assay has been optimized for formalin-fixed, paraffin-embedded tissue specimens. Optimum fixation should be between 6 and 48 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.

Supportive Data

Retrospective data was reviewed on 85 gastroesophageal tumors using the PathVysion HER2 probe set. The FISH results were compared to immunohistochemistry (IHC) testing. Of 36 specimens with HER2 amplification (ratio >2.2), 20 were 3+ by IHC, 8 were 2+, 1 was 1+, and 7 had unknown IHC results. Twenty-five normal gastric tissue control specimens were also tested. The correlation of FISH and IHC results are similar to those observed in validation studies for breast tumor specimens, so the interpretative guidelines will be the same.

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

1. Bang YJ, Van Cutsem E, Feyereislova A, ToGA Trial Investigators: 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, randomised controlled trial. Lancet 2010 Sep 3;376(9742):687-697

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

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