Germline E-cadherin gene mutations - Is prophylactic total gastrectomy indicated?

BACKGROUND. The CDH1 gene encodes E-cadherin, an epithelial cell adhesion m olecule. Germline CDH1 mutations recently were identified in families with hereditary diffuse gastric carcinoma in a pattern suggestive of autosomal d ominant inheritance with incomplete penetrance. METHODS, The proband was a woman age 47 years with a strong family history of diffuse gastric carcinoma. A germline E-cadherin gene mutation was ident ified in this patient, her brother, and three first cousins. ALL five famil y members underwent endoscopic evaluations, which were negative for maligna ncy, and elected to undergo a prophylactic total gastrectomy with Roux-en-Y esophagojejunostomy. RESULTS. Pathologic examination of the proband's stomach revealed several m icroscopic foci of intramucosal signet ring cell adenocarcinoma in the card ia and proximal gastric body. Postgastrectomy specimens from the proband's brother and three first cousins all showed intramucosal signet ring cell ad enocarcinoma in various regions of the stomach. Immunoperoxidase studies pe rformed on gastric tissue from these five patients demonstrated diminished or absent E-cadherin reactivity in the cancerous mucosa. CONCLUSIONS, Although total gastrectomy was performed as a prophylactic int ervention, occult gastric carcinoma was discovered in all five patients. Th us, total gastrectomy should be curative for gastric carcinoma in these pat ients. Based on their successful outcomes and the lack of efficacious surve illance methods for diffuse gastric carcinoma, prophylactic total gastrecto my may be the management of choice for germline E-cadherin gene mutation ca rriers. However, prophylactic total gastrectomy should be undertaken cautio usly because the procedure may be associated with considerable morbidity. C ancer 2001;92:181-7. (C) 2001 American Cancer Society.