Amplification of the HER-2/neu protooncogene in human endocrine tumors

Background. Amplification of HER-2/neu, a protooncogene related to the epidermal growth factor receptor, has prognostic significance in patients with breast cancer. Alterations in protooncogenes have not been determined for endocrine tumors in which prognosis is difficult to predict. We have addressed the question of whether amplification of HER-2/neu or epidermal growth factor receptor occurs in DNA from human endocrine tumor lines and have sought to characterize the HER-2/neu gene and its products in carcinoid tumors of the gut. Methods. The differential polymerase chain reaction procedure was used to detect genomic amplification in DNA samples from human endocrine tumor cell lines (BON, SIM, STAN) and from paraffin-embedded samples of carcinoid tumors. Sequencing techniques were used to determine whether mutations of the transmembrane domain of HER-2/neu existed. We then further characterized the gene products (RNA and protein) in carcinoid tumors. Results. Amplification of HER-2/neu was identified in all three endocrine tumor cell lines. HER-2/neu amplification was found in four of 10 carcinoid tumors of the gut; three of these four tumors were invasive or metastatic. In addition, HER-2/neu mRNA and protein were expressed in carcinoid tumors. Conclusions. Amplification of the HER-2/neu protooncogene occurs in endocrine tumors of the gut; quantitation of the actual copy number may be an important prognostic determinant. The unique human endocrine cell lines, established in our laboratory, will be useful models to further examine the significance of alterations of the HER-2/neu gene in endocrine tumors.