AB043. SOH24AB_263. CDH-1 mutation carriers: an institutional experience

Background: Gastric cancer is the third leading cause of cancer deaths worldwide. Most cases are sporadic, with 10% demonstrating familial clustering. Of these, 1–3% arise from inherited cancer syndromes. Hereditary diffuse gastric cancer was first described in 1964 in 3 Māori families from New Zealand. In 1998, Guilford et al. discovered a that these families carry a germline mutation in the tumour suppresser gene CDH1, encoding E-cadherin. Germline loss of E-cadherin expression increases the lifetime risk of developing diffuse gastric cancer and lobular breast cancer. The 2020 guidelines from the International Gastric Cancer Linkage Consortium recommend prophylactic total gastrectomy as the definitive intervention in individuals carrying the CDH1 mutation. In individuals not undergoing prophylactic total gastrectomy, endoscopic surveillance is recommended using the Cambridge protocol.

Methods: We followed all patients (n=16) identified with a CDH1 mutation. Patient demographics and clinicopathological factors were collected on all patients.

Results: We have identified four clusters of families with a CDH1 mutation. A total of six patients underwent a prophylactic total gastrectomy. All these patients had foci of signet ring cell carcinoma in the final histology. Eight patients have opted for close endoscopic surveillance as per the Cambridge protocol. Two further patients are due to have a prophylactic total gastrectomy (one due to an incidental endoscopic finding of a foci of signet ring cell carcinoma).

Conclusions: In the era of easily accessible genetic testing, increased knowledge of CDH1, its risks, and appropriate management, enable surgical prevention of gastric cancer in a subpopulation of patients.

Keywords: CDH1; gastric cancer; breast cancer; genetics; gastrectomy