Amplification and overexpression of the erbB-2 gene in human tumors: its involvement in tumor development, significance as a prognostic factor, and potential as a target for cancer therapy.

Abstract

The erbB-2 gene is amplified in a high percentage of human adenocarcinomas arising at numerous sites including breast, ovaries, lung, stomach and salivary gland. Gene amplification leads to overexpression of the protein, a member of the receptor tyrosine kinase family. A number of clinical studies have attempted to correlate the presence of high erbB-2 protein levels in tumors with poor patient prognosis. The majority of the studies do show a positive correlation suggesting that erbB-2 gene amplification and overexpression are signs of more aggressive tumors. The elevated levels of the erbB-2 protein, its extracellular accessibility, and its involvement in the malignant process make it an excellent candidate for tumor specific therapeutic agents.