Patients with advanced gastroesophageal cancer have poor survival with current therapy. Human epidermal growth factor receptor 2 (HER2) represents a promising therapeutic target, but the optimal HER2 testing strategy is not yet defined.
To evaluate the concordance between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) and to determine if the American Society of Clinical Oncology/College of American Pathologists HER2 scoring system is applicable to gastroesophageal carcinomas.
Formalin-fixed paraffin-embedded tumor samples from patients with advanced stage gastroesophageal cancer were tested by IHC and FISH and scored according to the American Society of Clinical Oncology/College of American Pathologists criteria for breast cancer. Concordance between IHC and FISH was evaluated. A subset of cases was subjected to array comparative genomic hybridization to verify the positive and negative HER2 results.
A total of 135 cases with paired IHC and FISH results were evaluated. The majority of samples (84%) were biopsies. HER2 amplification was detected in 20 tumors (15%). Using the American Society of Clinical Oncology/College of American Pathologists scoring system, IHC-FISH concordance was 97% for IHC 0, 93% for IHC 1+, and 100% for IHC 3+. Human epidermal growth factor receptor 2 positivity was strongly associated with tumor grade (moderately differentiated > poorly differentiated, P < .001) and histologic subtype (intestinal > diffuse, P  =  .007). Array comparative genomic hybridization analysis was successful in 31 tumors (14 FISH+ and 17 FISH-). Fluorescence in situ hybridization and array comparative genomic hybridization results were highly concordant in both HER2-positive and HER2-negative groups (93% and 100% concordance, respectively).
Human epidermal growth factor receptor 2 testing in gastroesophageal cancer can be performed using standard breast cancer procedures and the American Society of Clinical Oncology/College of American Pathologists scoring criteria. Although IHC 0 and IHC 3+ provide clear stratification, reliable separation of IHC 1+ and IHC 2+ may be difficult, especially in biopsy samples. The latter 2 groups are best referred to FISH for definitive classification.