The Heterogeneity of HER2 Expression in Esophageal and Gastric Adenocarcinomas
Brooke R Koltz, David G Hicks, Christa L Whitney-Miller. University of Rochester Medical Center, Rochester, NY
Background: The success of HER2-targeted therapy in the treatment of HER2 positive breast cancer has sparked interest in expanding the indications for this treatment in other solid tumors. Recent studies have shown that a subset of upper GI tract adenocarcinomas over-express the HER2 protein, and these patients will have increased overall survival when the HER2 targeted therapy, Trastuzumab, is added to chemotherapy. Correct identification of HER2 positive cancers in the upper GI tract has now become essential in order to stratify patients for therapy. The objective of this study is to further characterize the demographics of cases with HER2 expression, determine the extent of heterogeneity and its potential implications for HER2 testing strategies in these tumors.
Design: A retrospective review of gastric and esophageal adenocarcinoma biopsy and resection cases was prepared by searching the pathology archives for a 5 year period. Appropriate blocks were chosen for HER2 analysis. When available, 2 separate blocks containing tumor and lymph node metastases were chosen. Analysis of the IHC data (HercepTest, DAKO) and tumor demographics was performed. A subset analysis was performed on patients with IHC and corresponding FISH data.
Results: 176 patients were included in the study. 92 (52%) cases were adenocarcinomas arising in the esophagus, 80 (46%) arose in the stomach, and 4 (2%) cases were metastatic from either site. Overall, 21 (12%) of cases were positive for HER2 expression by IHC. HER2 positivity was more often seen in cases arising in the esophagus and in those with intestinal differentiation (p=0.02 and 0.21, respectively). Of the 103 cases with 2 or more blocks, discordant IHC results between blocks of 1 score or more were seen in 18 (17%) cases. Of those discordant cases, 14 (78%) patients would have had a change in HER2 status or needed additional HER2 FISH testing if only one block had been tested. In the subset population, 7 of 30 (23%) patients showed discordant results between the IHC and FISH testing. In 3 of the discordant cases, IHC staining on an additional block revealed concordant results with the FISH result.
Conclusions: HER2 expression is present in a subset of esophageal and gastric carcinomas, and significant heterogeneity was a frequent finding in these cases. Of the cases displaying heterogeneity, staining of multiple blocks for HER2 expression revealed a change in HER2 status in more than 75% of patients. These results indicate that IHC staining on a single block or on initial biopsy may not be sufficient for treatment stratification in upper GI adenocarcinoma patients.
Monday, March 19, 2012 1:00 PM
Poster Session II # 96, Monday Afternoon