Scientific Publications

Categorized: Gastroenterology

HER2 Testing: A New Hope for Patients with Gastric and Gastro-Esophageal Adenocarcinoma

Gastric cancer is associated with substantial morbidity and mortality worldwide. It is the second most common cause of cancer-related deaths globally.1 In the United States, the majority of patients with gastric cancer present with advanced, metastatic, or inoperable disease, and typically require chemotherapy.2

HER2 as a therapeutic target

HER2 is a key driver of tumorigenesis. Its overexpression as a result of HER2 gene amplification has been observed in a number of solid tumors. The most notable of these is breast cancer, for which HER2 is now a well-established therapeutic target for the drug Trastuzumab (Herceptin®).3 Testing for HER2 overexpression to identify breast cancer patients who could benefit from Herceptin® is now becoming the standard of care.4

Recent studies have demonstrated that HER2 is also an important biomarker in gastric and gastro-esophageal junction (GEJ) adenocarcinomas. Analysis of HER2 status by immunohistochemistry and in situ hybridization techniques have shown that HER2 is overexpressed up to 34% of gastric tumors.5

Trastuzumab (Herceptin®) for Gastric
Cancer Study (ToGA trial)

Results from the international, randomized, Phase III Trastuzumab for Gastric cancer study (ToGA trial) demonstrated a clear survival benefit from the addition of Trastuzumab (Herceptin®) to the therapy of those patients with advanced gastric or GEJ junction adenocarcinoma that exhibits HER2 overexpression.6 Patients with high HER2-expressing tumors derived the greatest benefit from trastuzumab therapy (Herceptin®). HER2 positivity can be established by immunohistochemistry and/or fluorescence in situ hybridization (FISH).

On the basis of these findings, FDA approval for trastuzumab was granted for patients with advanced gastric or GEJ junction adenocarcinoma when HER2-positivity was determined using approved testing methods. Given that the vast majority of patients with gastric/GEJ adenocarcinoma present with advanced/metastatic disease (>70% based on the SEER data for gastric cancer 2002-2008), a panel of experts recommended that “all patients with gastric cancer should be tested for HER2 status at the time of initial diagnosis, with biopsies being the preferred specimen type due to specimen quality reasons.”7

Inform Diagnostics is excited to announce the initiation of a new testing protocol that will aid in the management of patients with gastric and GEJ adenocarcinoma. We will be performing HER2 testing by both IHC and FISH on all patients with gastroesophageal adenocarcinomas (see figures 1 and 2).

Figure 1. Immunohistochemical stain for HER2 showing strong (3+) staining.

Figure 2. FISH for HER2/neu amplification.

We believe that your patients will benefit from this new test offering. Inform Diagnostics plans to continue to be at the forefront of molecular testing. And as always, we will only offer those tests that have clinical value and scientific merit. You will be notified about additional tests as they become available and as the scientific literature warrants. Please call 866-588-3280 if you have any additional questions.

– Ahmed Bedeir, MD, GI Pathologist


1 Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 2006; 24: 2137–50.

2 Cunningham D, Allum WH, Stenning SP, et al for the MAGIC trial participants. Perioperative chemotherapy versus surgery alone for resectable gastro-esophageal cancer. N Engl J Med 2006; 355: 11–20.

3 Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005; 353: 1659–72.

4 Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344: 783–92.

5 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.

6 Bang Y-J, Van Cutsem E, Feyereislova A, et al for the 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; 376: 687–97.

7 Rüschoff J, Hanna W, Bilous M, et al. HER2 testing in gastric cancer: a practical approach. Modern Pathology advance online publication 6 January 2012; doi: 0.1038/modpathol.2011.198.