The risk of GC incidence and mortality has declined in most country, but an acceptable overall five-years survival (52%) has been reached only in Japan, due to the mass screening that has led to early discovery. A reliable prognostic marker, could guide the therapeutic strategy, to provide a molecular target for therapies and act as a classic tumor marker in follow up, is strongly felt. E-cadherins (E-cad) could be such marker.
E-cad is an adhesine, expressed in the adherent junction of epithelial cells. The mutation or deletion of the E-cad gene (CDH1) has been found in some familial cancers but is common even in many sporadic cancers and is associated with poorly differentiated histotypes and poor prognosis. Many studies have indagated its reliability as tissutal and serum marker but the large variety of methods of evaluation of E-cad expression makes difficult to compare the results.
Nevertheless the role of E-cad appears very interesting.
Once excluded the specific issue related with familial GC, where in the presence of suspected familial GC, after an anamnestic careful screening, CDH1 test may identify the subset of patients in whom an early prophylactic total gastrectomy could reverse a fatal destiny, E-cad shows a particular clinical interest in three principal setting:
1)    In early GC, on biopsy sample, together with other imaging technique, might identify the cases that, although apparently favourable, could benefit from a more aggressive lymphadenectomy.
2)    As soluble marker might be of help in follow up, providing a reliable clue for early diagnosis of recurrence. Thus further studies are needed to validate the efficacy of this marker.
3)    In the future, a targeted therapy could achieve the results that are still now forbidden to surgery because of a late diagnosis.