AimsHER2 gene amplification has been detected in 10–20% of gastric adenocarcinomas. In view of the recently demonstrated clinical benefit of the anti-human epidermal growth factor receptor 2 (HER2) drug trastuzumab in the treatment of advanced gastric cancer, reliable HER2 testing is of key importance. The aim of this study was to examine HER2 status in gastro-oesophageal adenocarcinomas comparing SP3 and 4B5 immunohistochemistry (IHC) with dual probe HER2 [fluorescence in situ hybridization (FISH) and silver in situ hybridization (SISH)].Methods and resultsIHC and SISH were carried out on biopsy specimens of 146 patients with adenocarcinomas of the oesophagus and stomach. All SP3-IHC-positive cases and 91% of 4B5-IHC-positive cases were amplified. Sensitivity of SP3-IHC-positivity and 4B5-IHC-positivity for amplification was 77% and 96%, respectively. Results of FISH performed in 42 cases were identical to SISH. Amplification was heterogeneous in 73% of the adenocarcinomas; 24% of the oesophago-gastric carcinomas and 7% of distal stomach tumours were amplified.ConclusionsHER2-positivity is present in a significant proportion of oesophago-gastric adenocarcinomas (24%), but at a lower rate in the distal stomach (7%). Sensitivity for amplification is higher with 4B5 IHC than with SP3. FISH and SISH yield identical results, but assessment is much easier with SISH. Our findings provide important guidance for HER2-testing in gastro-oesophageal adenocarcinomas for patients in whom anti-HER2 treatment is considered.
e15555 Background: In the industrialized world, the incidence of adenocarcinomas of the distal esophagus/gastric cardia is increasing rapidly and though the incidence of carcinomas of the gastric body / antrum are decreasing they still represent a significant health problem. Several reports claim a significant HER2-positivity in gastro-esophageal adenocarcinomas. A large phase III trial in which HER2-positive gastric cancer patients are treated with trastuzumab is ongoing. New HER2 assessment methods are gaining popularity in breast cancer. Methods: HER2 status was examined in gastro-esophageal carcinomas, comparing SP3 (Labvision) and 4B5 (Ventana) immunohistochemistry (IHC), conventional dual probe HER2 FISH (DAKO), and SISH (Ventana) in a single Dutch institution. Results: IHC was carried out on biopsies of 146 patients with adenocarcinomas of the esophagus (n=44), gastric cardia (n=28), body (n=24) and antrum (n=50). IHC positivity, as defined by an immunoscore 2+ or 3+ using a modified scoring system, was present in 17 cases with the SP3 antibody, and in 24 cases with 4B5. FISH/SISH showed identical results in 40 cases carried out when any immunoreactivity in either antibody was detected. 100% of SP3-IHC-positive cases, and 92% of 4B5-IHC-positive were amplified. The negative predictive value of SP3 and 4B5 (immunoscores 0/1+) was 77% and 95%, respectively. Heterogenous HER2- positivity with partial staining/amplification was present in 73% of the adenocarcinomas, occasionally with only a tumor area of 10–20% showing positivity. HER2-amplification was present in 27% of esophageal and 18% in gastric cardia carcinomas (resulting in 24% amplification of tumors of the esophago-gastric region). In the distal stomach, 7% HER2-amplification was seen. Conclusions: HER2 amplification is present in a significant proportion of esophago-gastric region adenocarcinomas (24%) but at a much lower rate in the distal stomach (7%). Both antibodies can be used for initial screening for possible amplification though the 4B5 antibody has the highest negative predictive value. FISH and SISH yield identical results but the SISH assay offers rapid assessment. [Table: see text]
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