Summary
At the USCAP 2026 meeting, two guidelines on gastrointestinal pathology biomarkers will be presented. The updated guideline on HER2 testing in gastroesophageal adenocarcinoma reaffirms IHC with follow-up ISH as the best method for determining HER2 status. It also recommends testing the highest-quality tumor specimen, preferably the metastasis, and emphasizes the importance of considering tumor heterogeneity when selecting specimens for testing.
Charna Albert
February 2026—At USCAP 2026 next month in San Antonio, two guidelines on the use of gastrointestinal pathology biomarkers will take the stage in the CAP companion society session.
One is a new CAP guideline that will help pathologists and their clinical colleagues evaluate Ki67 in gastroenteropancreatic neuroendocrine tumors. The other is an updated version of the CAP guideline on HER2 testing in gastroesophageal adenocarcinoma, published in 2016. Both will be submitted for publication this year to the Archives of Pathology & Laboratory Medicine.
At its core, little has changed with the update to the guideline on HER2 in GEA. The Trastuzumab for Gastric Cancer (ToGA) trial is still the basis for the guideline’s HER2 recommendations.
“It was a good time to look at the literature on gastric and esophageal HER2 and see if anything had changed about the original recommendations, and our core recommendations for pathologists are unchanged,” says Mary Kay Washington, MD, PhD, professor of pathology, microbiology, and immunology at Vanderbilt University Medical Center and a member of the expert panel that authored the guideline update.
Nevertheless, there were pressing things to address with the update. Front of mind for Amy Brownlee, MD, who coauthored the guideline and will present it at the USCAP meeting, was reaffirming that IHC with follow-up ISH as needed is the best test for HER2 in patients with advanced GEA. “There is a large number of molecular diagnostic tests that oncologists use, many of which include determination of HER2 copy number variation,” says Dr. Brownlee, assistant professor of pathology and laboratory medicine at the University of North Carolina School of Medicine. These assays, however, are not as reliable as the IHC/ISH panel approach. The updated guideline, she says, should help communicate to pathologists and oncologists at large that “this is still the best way to determine HER2 status.”
One departure from 2016: The American Society of Clinical Oncology, a full partner in 2016, was not involved with the guideline update. “The medical oncology side of it had equal emphasis in the original guideline,” Dr. Washington says, “and since then this has evolved into a mostly pathology-focused guideline,” led by the CAP in collaboration with the American Society for Clinical Pathology.
The updated guideline establishes a trio of new recommendations. The first recommendation says pathologists should request HER2 testing on the highest-quality tumor specimen, whether primary or metastasis. “Ideally, we should be testing the metastasis because that’s what’s going to need to be treated,” Dr. Washington says. “But common sense and judgment should prevail on specimen selection. If you have a necrotic specimen from a met and you don’t have many cells to look at, you will not have confidence in your results necessarily.” Testing a higher-quality specimen as well as the metastasis would be appropriate in such a situation, she adds.
Pathologists should select the tissue block with the areas of lowest-grade tumor morphology in biopsy, resection, or fine-needle aspiration specimens, the recommendation says. More than one tissue block may be selected if different morphological patterns are present. Generally, the more well-differentiated areas should be tested, Dr. Brownlee says. “But if you see multiple morphologically distinct regions, it’s good to test all of those for HER2.”