Gene Amplification in Gastric and Esophageal Adenocarcinomas1

In a United States series of 28 gastric/esophageal adenocarcinomas of poorly to moderately differentiated histopathology, we detected gene amplification in 21% of the tumors. Using the modified DNA in-gel renaturation assay to detect down to 7-8 copies of amplified DNA sequences, we identified 3 gastric tumors with amplified DNA sequences and confirmed by Southern hybridization analysis that I IKR-2/nc«was amplified >5-fold in these specimens. Immunohistochemical staining of tumor tissue sections with pl85 HER-2/neu antibodies demonstrated that only the 3 gastric adenocarcinomas with corresponding HER-2/neu gene amplification displayed membrane immunoreactivity. Amplification of cmtt was identified in 2 tumors, and this was the first study to assay for multiple copies of this protooncogene in fresh gastric tumor tissues. Amplification of v-frhtt was observed in one tumor, and no evidence for amplification of int-2 was obtained in this series of adenocarcinomas. We have recently observed dmins in gastric and lower esophageal adenocarcinomas providing evidence for gene amplifica tion (23). Multiple copies of HER-2/neu (17, 24), c-myc (25), c-yes-l (26), c-ras-Ki (27), Int-2/hst-l (28, 29), and c-erbB (16) have previously been reported in gastric and esophageal squamous cell carcinomas and adenocarcinomas of mixed histolÃ3g ica! types. In order to assess the incidence of gene amplification and ultimately to correlate amplification with clinical outcome, we examined 28 cases of gastric and lower esophageal adeno carcinomas in patients in the United States for the presence of amplified DNA sequences using the in-gel renaturation assay and Southern hybridization analysis. We observed amplifica tion in 21% of tumors and confirmed that HER-2/neu and occasionally c-met and c-erbE were amplified in these tumors.