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

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• 作者：Rudolf Repak ; MD¹ ; Darina Kohoutova ; MD ; PhD¹ ; ² ; ; Miroslav Podhola ; MD ; PhD³ ; Stanislav Rejchrt ; Prof ; MD ; PhD¹ ; Marek Minarik ; Dr ; PhD⁴ ; ⁵ ; Lucie Benesova ; Dr ; PhD⁴ ; Michal Lesko ; MD ; PhD⁶ ; Jan Bures ; Prof ; MD ; PhD ; FCMA¹
• 关键词：FAP ; familial adenomatous polyposis ; FIGC ; familial intestinal gastric cancer ; GAPPS ; gastric adenocarcinoma and proximal polyposis of the stomach ; HDGC ; hereditary diffuse gastric cancer ; NGS ; next-generation sequencing ; PCR ; polymerase chain reaction ; PPI ; proton pump inhibitor ; YY1 ; Ying Yang 1
• 刊名：Gastrointestinal Endoscopy
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：84
• 期：4
• 页码：718-725
• 全文大小：4433 K

文摘

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 Ying Yang 1 (YY1) binding motif in promoter 1B of the APC gene were assigned as causal in 6 families with GAPPS.

Methods

We diagnosed GAPPS across 3 generations in 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 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 specimens 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 specimens and genetic testing with recently discovered mutations in promoter 1B of the APC gene might help clinicians to decide whether prophylactic gastrectomy should be performed.