The first European family with gastric adenocarcinoma and proximal polyposis of the stomach: case report and review of the literature

Abstract Background and Aims Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) has to date been recognized in only 8 families worldwide. Recently, different point mutations within the YY1 binding motif in the promoter 1B of APC gene were assigned as causal in 6 families with GAPPS. Methods We diagnosed GAPPS across 3 generations of a Czech white family. Results The proband´s mother died of gastric cancer at 49 years of age. The proband died of gastric cancer at 56 years of age. All 3 of the proband´s daughters inherited polyposis, involving exclusively the gastric fundus and body, with relative sparing of the lesser curve. The daughters have all been regularly surveyed endoscopically. Polyposis progressed rapidly with intestinal differentiated low-grade and high-grade dysplasia being present on polypectomy specimens 5 years after the original diagnosis. On this basis, all 3 of the proband´s daughters were scheduled for prophylactic total gastrectomy. Unfortunately, the middle daughter presented with generalized gastric adenocarcinoma and died at the age of 26 years. The other 2 daughters (aged 30 and 23 years) underwent total gastrectomy within 6 weeks of their sister´s death; histology of surgical speciments showed gastric adenocarcinoma stage IA (pT1a, N0, M0) in both cases. Bi-directional Sanger sequencing of promoter 1B revealed a point mutation (c.-191 T>C) in all 3 daughters of the proband. Conclusions Atypical endoscopic progression of the fundic gland polyposis, with the presence of dysplasia on polypectomy speciments and genetic testing with recently discovered mutations in promoter 1B of APC gene might help the clinicians as to whether prophylactic gastrectomy should be performed.