HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma

Publication Date: December 1, 2016
Last Updated: March 14, 2022


In patients with GEA who are potential candidates for HER2-targeted therapy, the treating clinician should request HER2 testing on tumor tissue. (Strong recommendation)

Treating clinicians or pathologist should request HER2 testing on tumor tissue in the biopsy or resection specimens (primary or metastasis) preferably before the initiation of trastuzumab therapy if such specimens are available and adequate. HER2 testing on FNA specimens (cell blocks) is an acceptable alternative. (Recommendation)

Treating clinicians should offer combination chemotherapy and HER2-targeted therapy as the initial treatment for appropriate patients with HER2-positive tumors who have metastatic or recurrent GEA. (Recommendation)

Laboratories/pathologists must specify the antibodies and probes used for the test and ensure that assays are appropriately validated for HER2 IHC and ISH on GEA specimens. (Strong recommendation)

When GEA HER2 status is being evaluated, laboratories/pathologists should perform/order IHC testing first followed by ISH when IHC result is 2+ (equivocal). Positive (3+) or negative (0 or 1+) HER2 IHC results do not require further ISH testing. (Strong recommendation)

Pathologists should use the Ruschoff/Hofmann method in scoring HER2 IHC and ISH results for GEA. (Strong recommendation)

Pathologists should select the tissue block with the areas of lowest grade tumor morphology in biopsy and resection specimens. More than 1 tissue block may be selected if different morphologic patterns are present. (Recommendation)

Laboratories should report HER2 testing results in GEA specimens in accordance with the CAP “Template for Reporting Results of HER2 (ERBB2) Biomarker Testing of Specimens From Patients With Adenocarcinoma of the Stomach or Esophagogastric Junction.” (Strong recommendation)

Pathologists should identify areas of invasive adenocarcinoma and also mark areas with strongest intensity of HER2 expression by IHC in GEA specimens for subsequent ISH scoring when required. (Strong recommendation)

Laboratories must incorporate GEA HER2 testing methods into their overall laboratory quality improvement program, establishing appropriate quality improvement monitors as needed to ensure consistent performance in all steps of the testing and reporting process. In particular, laboratories performing GEA HER2 testing must participate in a formal proficiency testing program, if available, or an alternative proficiency assurance activity. (Strong recommendation)

There is insufficient evidence to recommend for or against genomic testing in patients with GEA at this time. (No recommendation)

Recommendation Grading



HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma

Authoring Organizations

Publication Month/Year

December 1, 2016

Last Updated Month/Year

January 16, 2024

Document Type


External Publication Status


Country of Publication


Document Objectives

To establish an evidence-based guideline for HER2 testing in patients with GEA, to formalize the algorithms for methods to improve the accuracy of HER2 testing while addressing which patients and tumor specimens are appropriate, and to provide guidance on clinical decision making

Inclusion Criteria

Female, Male, Adolescent, Adult, Child, Infant, Older adult

Health Care Settings

Hospital, Operating and recovery room, Outpatient, Radiology services

Intended Users

Laboratory technician, nurse, nurse practitioner, physician, physician assistant


Assessment and screening, Diagnosis, Management

Diseases/Conditions (MeSH)

D000230 - Adenocarcinoma


cancer, gastroesophageal adenocarcinoma, receptor tyrosine kinase 2

Source Citation

Angela N. Bartley, Mary Kay Washington, Christina B. Ventura, Nofisat Ismaila, Carol Colasacco, Al B. Benson III, Alfredo Carrato, Margaret L. Gulley, Dhanpat Jain, Sanjay Kakar, Helen J. Mackay, Catherine Streutker, Laura Tang, Megan Troxell, and Jaffer A. Ajani (2016HER2 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. Archives of Pathology & Laboratory Medicine: December 2016, Vol. 140, No. 12, pp. 1345-1363.


Number of Source Documents
Literature Search Start Date
January 1, 2008
Literature Search End Date
June 1, 2015