A comparison of the yield from endoscopic surveillance in detecting early gastric cancer in CDH1+ve versus CDH1-ve HDGC families


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Emma Mi1,Ella Mi1,Marc Tischkowitz2,Susan Richardson3,Massimiliano di Pietro4,Krish Ragunath5,Maria O’Donovan6,Rebecca Fitzgerald7
1University of Cambridge School of Clinical Medicine,2Department of Medical Genetics, University of Cambridge and Cambridge University Hospitals NHS Trust,3Familial Gastric Cancer Registry, Department of Oncology, Cambridge University Hospitals NHS Trust,4MRC Cancer Unit, Hutchison-MRC Research Centre, Cambridge,5Nottingham Digestive Diseases Centre, Nottingham University Hospitals NHS Trust,6Department of Histopathology, Cambridge University Hospitals NHS Trust,7MRC Cancer Cell Unit, University of Cambridge

Abstract

Background

Germline CDH1 (E-cadherin) mutation is present in 40% of individuals fulfilling the criteria for Hereditary Diffuse Gastric Cancer (HDGC) and confers 80% lifetime risk of gastric cancer. Current guidelines advise prophylactic gastrectomy for CDH1-positive individuals but endoscopic surveillance is recommended for patients delaying gastrectomy, due to comorbidity or psychosocial reasons, and for individuals from CDH1-negative families fulfilling HDGC criteria (van der Post et al J Med Genet 2015). This study aimed to determine the endoscopic yield of signet ring cell foci (SRCF) according to CDH1 mutation status.

Method

A prospective cohort study of 54 CDH1+ve and 31 CDH1-ve patients fulfilling HDGC criteria undergoing 175 endoscopies (CDH1+ve: 103; CDH1-ve: 72) according to the Cambridge HDGC protocol (van der Post et al 2015). The median (IQR) follow up, in months, was 16.0 (3.5-39.0) (CDH1+ve: 11.0 (3.0-28.3); CDH1-ve: 27.0 (7.0-48.0)). Data on patient age, gender, ethnicity, H. pylori status and PPI use was collected. The outcome was time to detection of SRCF from first endoscopy. Kaplan-Meier analysis with log rank test and Cox regression on CDH1 status, age and ethnicity were performed.

Results

Between the CDH1+ve and –ve group, there was no significant difference in gender (p=0.637), H. pylori status (p=0.094) or PPI use (p=0.810), but there was a significant difference in median age (34.5 vs 45, p=0.026) and ethnicity (18.5% vs 0% Asian, p=0.012). CDH1+ve patients had significantly higher progression to endoscopic detection of SRCF (p=0.000) than CDH1-ve patients, with over 12-fold increased risk of SRCF on endoscopy (HR 12.2, 95% Cl 2.8-52.8, p=0.001). On Cox regression, age (p=0.811) and ethnicity (p=0.733) were not associated with risk of SRCF. In the CDH1-ve group, only 2 related individuals ever had SRCF detected.

Conclusion

There is very low endoscopic yield of SRCF in CDH1-ve patients. The value and frequency of surveillance in this group should be reconsidered.