The HER-2/neu oncogene in tumors of the gastrointestinal tract

The HER-2/neu oncogene is localized to chromosome 17q and shares significan t homology with the epidermal growth factor receptor As a result of ifs pot ential role in the selection of therapy, HER-2/neu testing has reached near -standard-of-practice status in breast cancer: There is considerable intere st in HER-2/neu as a prognostic factor and target of therapy in tumors elf the gastrointestinal tract. In this review of HER-2/neu expression in esoph ageal squamous cell carcinoma and adenocarcinomas of the esophagus, stomach , and colon, a wide range of expression of HER-2/neu from 0 to 83% likely r eflects both differences in methods and reagents, as well as study bias ass ociated with patient selection (i.e., early versus advanced disease). For e sophageal squamous cell carcinoma, little information exists as to the prog nostic significance of HER-2/neu expression. In adenocarcinoma associated w ith Barrett's esophagus there is contradictory data. However, most of the i nformation available indicates that this marker hers significant prognostic value. In gastric adenocarcinoma, the wide expression range may truly refl ect patient selection because HER-2/neu positivity appears linked to advanc ed rather than early disease with limited invasion. The majority of studies favor a significant prognostic value of HER-2/neu status for this tumor: F inally in colorectal cancer HER-2/neu overexpression also appears to be a s ignificant adverse outcome indicator as judged by the current published lit erature. In conclusion, given that either HER-2/neu protein overexpression or gene amplification is associated with approximately one-fourth of all ga strointestinal tract malignancies, strategies designed to employ the marker therapy selection appear warranted. During the next several years it will not be surprising to see these tumors treated with antiHER-2/neu modalities such as Herceptin (TM), likely in combination with other agents initially Sor patients with advanced disease, and possibly, for individuals with high -risk lesions in an adjuvant? setting.