Prophylactic gastrectomy in hereditary diffuse type gastric cancer with E-cadherin germline mutation

H. Vogelsang, A. Neutzling, K. Ott, G. Keller

Research output: Contribution to journalArticlepeer-review

Abstract

Hereditary diffuse type gastric cancer (HDGC) can be caused by E-cadherin germline mutation. Following the first three papers in 1998/99 describing Neuzeeland as well as families of European origin prophylactic gastrectomies in the course of predictive molecular screening have been performed. Indication for genetic testing, family penetrance and calculated lifetime risk, effectivity of endoscopie screening, perioperative risk, and histological findings in macroscopic normal stomachs of germine mutation carriers define counselling and treatment of families with HDGC. Amongst 14 families tested at our laboratory we found one frameshift and one missense mutation so far. Within the International Gastric Cancer Linkage Consortium (IGCLC) 21 truncating and 6 missense mutations have been registered. Genetic testing for Ecadherin germline mutation should be performed in families with 3 histological proven diffuse type gastric cancer or 2, one younger 50 years, amongst first or second degree relatives. Incidence of mutation positive families is expected to be at least 30 percent. There is a broad experience on testing families with only one histological proven index case of diffuse type or intestinal type gastric cancer and a positive family history showing no identified E-cadherin germline mutations. Within the IGCLC 11 highly penetrant families with proven E-cadherin germline mutation showing an autosomal pattern were evaluated regarding penetrance. The estimated cumulative risk of gastric cancer by age 80 was 67% for men (annual risk 1.2%) and 83% for women. The combined risk of gastric cancer and breast cancer in women was 90%. The effectivity of en-doscopic screening to detect early gastric cancer is assumed to be low due to the diffuse type growth pattern underlying normal-appearing surface epithelium. Alternatively mortality of diffuse type gastric cancer has been high in HDGC families. Perioperative morbidity and mortality following RO-resection of gastric cancer with D2-lymphadenectomy at our own institution is less than 10% and 2% respectively in patients younger 40 years. Performing prophylactic gastrectomies on patients without apparent tumour disease rates should be even lower. Histological investigation of prophylactically removed stomachs in germline mutation carriers showed typical premalignant changes as well as in three cases multiple and in one case a single focus of early diffuse type gastric cancer. E-cadherin germline mutation carriers of high penetrant diffuse type gastric cancer families have a high lifetime risk of gastric cancer with little chance of effective early tumour screening. Early and multiple foci of diffuse type gastric cancer in macroscopically and endoscopically normal stomachs seem to justify an invasive prophylactic gastrectomy.

Original languageEnglish
Pages (from-to)476-477
Number of pages2
JournalLangenbeck's Archives of Surgery
Volume386
Issue number6
StatePublished - 2001
Externally publishedYes

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