Frequency and distribution of HER2 overexpression in advanced malignancies.

e21153 Background: Testing for HER2 has revolutionized the management of breast cancer and, now, gastro-esophageal junction cancer. The purpose of this study was to capture the relative frequency and distribution of HER2 overexpression in other cancers. Methods: In a cohort of 11,223 patient samples, HER2 was assayed by immunohistochemistry using the Ventana HER2 (4B5) antibody. Slides were then read by pathologists using the cutoff of (>=3+ and >=30% as positive) for HER2. In this same cohort, 2,246 patient samples underwent HER2 by FISH testing using Abbott’s Pathvysion HER2 assay. FISH analysis was interpreted by a cytogeneticist based on ASCO/CAP guidelines for breast cancer. Prior to the analysis, 4,116 patient samples were excluded secondary to an unknown tumor lineage or other lineage rarely seen in our laboratory. In all, twenty-seven tumor lineages comprising 7,107 patient specimens were analyzed. Results: Our preliminary observations indicated that the frequency of HER2 by IHC is highest in breast carcinoma (68.6%), colorectal adenocarcinoma (7.2%), ovarian surface epithelial carcinoma (5.4%), gastroesophageal adenocarcinoma (4.5%), non-small cell lung cancer (3.1 %), pancreatic adenocarcinoma (1.3%) and gastric adenocarcinoma (1.3%) In these same lineages, frequency of HER2 by FISH is highest in breast carcinoma (46.0%) followed by surface epithelial ovarian carcinoma (12.7%), non-small cell lung cancer (8.3 %), gastroesophageal adenocarcinoma (6.7%), gastric adenocarcinoma (4.8%), pancreatic adenocarcinoma (4.0%), colorectal adenocarcinoma (3.2%). Distributional differences in IHC versus FISH results were analyzed by Pearson’s chi-square (x2) test, with statistical significance (p<0.05) achieved in breast carcinoma, gastric adenocarcinoma, gastroesophageal adenocarcinoma and surface epithelial ovarian carcinoma. Conclusions: To our knowledge, this is the first study involving a large patient pool with advanced malignancies in which HER2 status was investigated in a single clinical laboratory with standardized IHC and FISH. This study shows that HER2 is frequently expressed in other cancer types, which merits the inclusion of therapeutic strategies using HER2-targeted therapy in such tumors.