NORTHFIELD, Ill. (October 21, 2026) — The updated testing guideline for advanced gastroesophageal adenocarcinoma (GEA) now recommends repeat human epidermal growth factor receptor 2 (HER2) testing for HER2-positive GEA patients being evaluated for second-line targeted therapy with disease progression.
The College of American Pathologists (CAP), in collaboration with the American Society for Clinical Pathology (ASCP), released updated evidence-based guidelines to support accurate and consistent HER2 testing in patients with advanced GEA.
HER2 testing in GEA remains complex due to tumor heterogeneity, variable specimen quality, and evolving testing approaches. Following advances since the guideline’s release in 2016, including expanded biomarker testing and HER2-targeted therapies, an expert panel conducted a systematic evidence review and issued three strong recommendations while reaffirming four prior recommendations as good diagnostic practice statements.
Key Updates and Recommendations
- Test the highest-quality tumor specimen at initial diagnosis.
HER2 testing should be performed on the best available tumor specimen, whether from the primary tumor or a metastatic site. When multiple tumor morphologies are present, testing more than one tissue block can be considered to help ensure accurate results. - Maintain IHC with reflex ISH when IHC result is 2+ as the preferred testing approach.
Immunohistochemistry (IHC), followed by in situ hybridization (ISH) when ISH is 2+ , remains the standard method for assessing HER2 status in GEA. While genomic testing—on tissue or blood—may provide complementary information, it should not replace IHC/ISH due to lower sensitivity and variable concordance. - Consider repeat HER2 testing at disease progression.
For patients with previously HER2-positive advanced GEA who are being evaluated for second-line HER2-targeted therapy, repeat HER2 testing may be performed on relapsed or recurrent tumor tissue. Liquid biopsy may be used when tissue sampling is not feasible.
This represents a change from the 2016 guideline, which recommended retesting in the majority of cases. By clarifying when repeat testing is appropriate, this guideline supports informed clinical decision-making and improves patient care.
For tools, resources, and further details, visit the guideline webpage on cap.org.
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About the College of American Pathologists
As the world’s largest organization of board-certified pathologists and leading provider of laboratory accreditation and proficiency testing programs, the College of American Pathologists (CAP) serves patients, pathologists, and the public by fostering and advocating excellence in the practice of pathology and laboratory medicine worldwide.