title: A prospective study of total gastrectomy for CDH1-positive hereditary diffuse gastric cancer.
abstract: BACKGROUND
  Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer syndrome. Up to 30% of families with HDGC have mutations in the E-cadherin gene, CDH1. The role of prophylactic versus therapeutic gastrectomy for HDGC was studied prospectively.
  
  
  METHODS
  Eighteen consecutive patients with CDH1 mutations and positive family history were studied prospectively, including 13 without and 5 with symptoms. Proportions were compared by Fisher's exact test, and survival by the Breslow modification of the Wilcoxon rank-sum test.
  
  
  RESULTS
  Each patient underwent total gastrectomy (TG), and 17 (94%) were found to have signet ring cell adenocarcinoma. Twelve of 13 asymptomatic patients had T1, N0 cancer, and only 2/12 (16%) had it diagnosed preoperatively despite state-of-the-art screening methods. Each asymptomatic patient did well postoperatively, and no patient has recurred. For five symptomatic patients, each (100%) was found to have signet ring cell adenocarcinoma (P = 0.002 versus asymptomatic) by preoperative endoscopy; three (60%) had lymph node involvement and two (40%) had distant metastases at time of operation. Two-year survival was 100% for asymptomatic and 40% for symptomatic patients (P < 0.01).
  
  
  CONCLUSIONS
  The data show that asymptomatic patients with family history of HDGC and CDH1 mutation have high probability of having signet ring cell adenocarcinoma of the stomach that is not able to be diagnosed on endoscopy; when symptoms arise, the diagnosis can be made by endoscopy, but they have metastases and decreased survival. Surveillance endoscopy is of limited value, and prophylactic gastrectomy (PG) is recommended for patients with family history of HDGC and CDH1 mutations.
authors.affiliation: Departments of Surgery, Stanford University School of Medicine, Stanford Comprehensive Cancer Center, Stanford, CA, USA.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Chen
authors.forename: Kerry
authors.initials: K
authors.lastname: Kingham
authors.forename: James M
authors.initials: JM
authors.lastname: Ford
authors.forename: James
authors.initials: J
authors.lastname: Rosing
authors.forename: Jacques
authors.initials: J
authors.lastname: Van Dam
authors.forename: R Brooke
authors.initials: RB
authors.lastname: Jeffrey
authors.forename: Teri A
authors.initials: TA
authors.lastname: Longacre
authors.forename: Nicki
authors.initials: N
authors.lastname: Chun
authors.forename: Allison
authors.initials: A
authors.lastname: Kurian
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Norton
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics*; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D005743:Gastrectomy; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011379:Prognosis; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D015996:Survival Rate; D055815:Young Adult
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins