[Diffuse stomach carcinoma: from H&E diagnosis and molecular pathology to specific therapy]

E-cadherin is a homophilic cell adhesion molecule that is mutated in half of diffuse-type gastric cancer patients. Since these mutations generally affect the extracellular portion of the transmembrane molecule and do not interrupt the reading frame, altered E-cadherin protein may be an excellent tumor marker. We established a rapid PCR-based E-cadherin mutation detection technique allowing positive results within a day. Furthermore, we succeeded in the generation of monoclonal antibodies that specifically react with mutant E-cadherin but not with the wild-type protein. In gastric carcinoma specimens known to express mutant E-cadherin messenger RNA these monoclonal antibodies target exclusively tumor cells in routine formalin fixed and paraffin embedded material from biopsies, primary tumors and lymph node metastases. Non-tumorous cells, including normal gastric epithelium expressing wild-type E-cadherin, are not stained. The unique type of E-cadherin mutations in diffuse-type gastric cancer (missense mutations and complete or partial in-frame deletions of exons) might improve the information of conventional diagnostic techniques. In addition, they may open novel and more selective clinical avenues to treat small tumor deposits for adjuvant-, neoadjuvant- and additive-therapy.