Global distribution of prophylactic total gastrectomy in E-cadherin (CDH1) mutations.

Individuals with germline E-cadherin (CDH1) mutations are at high risk of developing diffuse gastric cancer (GC) and prophylactic total gastrectomy (PTG) represents the only life-saving treatment. We reviewed all PTGs reported in literature associated with CDH1 germline mutations. A total of 224 PTGs were reported. The majority were described in the United States of America (50%), the Netherlands (17.8%), and Canada (12.5%). GC was identified in 85.4% of cases after PTG, with a high rate of "no cancer" at histopathology identified in the United States of America (19.6%). Considering the mutation type, a total of 61 different germline mutations was reported, primarily non-missense versus missense alterations (86.9% v 13.1%). Twenty-one PTGs were performed in individuals with no family history of GC, and tumor was detected in 33.3% of investigated cases; regarding individuals with a family history of GC, tumor was identified in 85% of cases. PTG remains the best treatment for individuals harboring germline CDH1 mutations and fulfilling specific clinical criteria; in other CDH1-associated conditions, PTG should be suggested, but not strongly recommended. Additional studies are required to assess the cancer risk in those conditions.