Interpretive Handbook

Test 60620 :
HER2 Amplification Associated with Gastroesophageal Cancer, FISH, Tissue

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 human epidermal growth factor receptor 2 (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 or overexpression may be candidates for treatment with the drugs that target the HER2 protein or its downstream pathways (eg, trastuzumab [Herceptin], pertuzumab, lapatinib).

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

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, lapatinib)


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

Interpretation Provides information to assist in interpretation of the test results

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, and the guidelines used by the ToGA trial.


Specimens with equivocal results as defined by 2013 ASCO/CAP guidelines will have reflex testing performed using the HER2/D17S122 probe. The report will include a complete interpretation including the HER2:D17Z1 and HER2:D17S122 results.


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 gastroesophageal tumors.

-For breast tumors, order FHER2 / HER2 Amplification Associated with Breast Cancer, FISH, Tissue.

-For urothelial tumors, order FH2UR / HER2 Amplification Associated with Urothelial Carcinoma, 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.


The assay has been optimized for formalin-fixed, paraffin-embedded tissue specimens. 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.

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.

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

1. 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, randomised controlled trial. Lancet 2010;376(9742):687-697

2. 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

3. 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

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