Germline E-cadherin gene mutations

Abstract

BACKGROUND The CDH1 gene encodes E‐cadherin, an epithelial cell adhesion molecule. Germline CDH1 mutations recently were identified in families with hereditary diffuse gastric carcinoma in a pattern suggestive of autosomal dominant 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 identified in this patient, her brother, and three first cousins. All five family members underwent endoscopic evaluations, which were negative for malignancy, and elected to undergo a prophylactic total gastrectomy with Roux‐en‐Y esophagojejunostomy. RESULTS Pathologic examination of the proband's stomach revealed several microscopic foci of intramucosal signet ring cell adenocarcinoma in the cardia and proximal gastric body. Postgastrectomy specimens from the proband's brother and three first cousins all showed intramucosal signet ring cell adenocarcinoma in various regions of the stomach. Immunoperoxidase studies performed 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 intervention, occult gastric carcinoma was discovered in all five patients. Thus, total gastrectomy should be curative for gastric carcinoma in these patients. Based on their successful outcomes and the lack of efficacious surveillance methods for diffuse gastric carcinoma, prophylactic total gastrectomy may be the management of choice for germline E‐cadherin gene mutation carriers. However, prophylactic total gastrectomy should be undertaken cautiously because the procedure may be associated with considerable morbidity. Cancer 2001;92:181–7. © 2001 American Cancer Society.