The use of molecular biology in diagnosis and prognosis of gastric cancer

The investigation of molecular and genetic changes in gastric cancer has br ought new insights into the pathogenesis of the disease. Knowledge of the g enetic abnormalities and altered molecules could be used for differential d iagnosis in case of an unknown primary tumor, allows their evaluation as pr ognostic factors, and could open novel avenues for more specific clinical i nterventions. Clinically relevant molecules whose expression or structure i s altered include the plasminogen activator and its inhibitor plasminogen a ctivator inhibitor type 1, the cell cycle regulator cyclin E, epidermal gro wth factor, the apoptosis inhibitor bcl-2, the cell adhesion molecule E-cad herin, and the multifunctional protein beta-Catenin. In addition, genetic i nstability is commonly seen. Gene amplification and protein overexpression of the growth factor receptors c-erbB2 and K-sam may be prognostic factors for intestinal- and diffuse-type gastric cancer, respectively. There has lo ng been evidence for a genetic predisposition to gastric cancer by epidemio logical studies and case reports. Very recently, germ line mutations of E-c adherin have been identified that are responsible for a dominantly inherite d from of diffuse-type gastric cancer and could be used to identify individ uals that are at high risk. The clinical implications of the recent finding s for diagnosis, prognosis, therapy, and risk assessment are discussed. (C) 2000 Elsevier Science Ltd. All rights reserved.