HER2 Status in 146 Gastroesophageal Carcinomas Assessed by Two Rabbit Monoclonal Antibodies (SP3 and 4B5) and Two In Situ Hybridisation Methods (FISH and SISH)
JE Boers, JC Meeuwissen, N Methorst. Isala Klinieken, Zwolle, Netherlands
Background: The incidence of adenocarcinomas of the distal esophagus / gastric cardia is rapidly increasing. Though the number of carcinomas of the gastric body / antrum are decreasing in the industrialized world, these tumors still represent a significant health problem. In recent years, HER2 has emerged as a routinely performed predictive test in breast cancer. Several reports claim significant HER2-positivity in gastro-esophageal adenocarcinomas. At present, a large phase III trial in which HER2-positive gastric cancer patients are treated with trastuzumab a therapeutic anti-HER2 antibody - is ongoing. New HER2 assessment methods using were introduced recently and are gaining popularity in breast cancer.
Design: 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 Dutch population from a single 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 only 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 rabbit monoclonal antibodies SP3 and 4B5 can be used for initial screening for possible amplification though the 4B5 antibody has the highest negative predictive value. FISH and SISH yields identical results. The SISH assay offers a easy and fast assessment. The possible role for HER2 as a predictive test for trastuzumab therapy in gastric cancer will be established in the near future.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 99, Wednesday Afternoon