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149 E-CADHERIN AND HEREDITARY DIFFUSE GASTRIC CANCER: TWO CASES, CLINICAL REVIEW AND DISCUSSION OF MANAGEMENT OPTIONS C Teshima, D Gilchrist, E Lalor AIMS: Hereditary diffuse gastric cancer (HDGC) is caused by a germline mutation in the CDH-1 gene encoding e-cadherin. The mutation confers up to an 80% lifetime risk of developing this familial form of gastric cancer. We present a patient with a significant family history of diffuse gastric cancer and a second patient with a confirmed gene mutation. We then describe the clinical features and natural history of patients with the e-cadherin mutation before reviewing the management options and endoscopy surveillance strategies available.
University of Alberta, Edmonton, Alberta
METHODS: A literature search was performed on MEDLINE using the following search terms: hereditary diffuse gastric cancer, cadherins, e-cadherin mutation, CDH1 mutation, carcinoma signet ring cell, prophylactic gastrectomy, congo red, chromoendoscopy. Additional relevant articles were obtained by inspecting the reference lists of previously identified papers. In addition, surveillance endoscopy was performed on the second patient.
RESULTS: The risk of gastric cancer with this mutation is estimated at 83% for women and 67% for men by age 80, with a mean age of 40. The cancer begins as multiple foci of signet ring cell carcinoma lying beneath normal gastric epithelium. There is a prolonged indolent phase before it develops into advanced cancer. The current recommendation is that patients undergo prophylactic gastrectomy to eliminate their risk. This is based on studies that demonstrated the presence of gastric cancer in gastrectomy specimens from patients in whom no evidence of carcinoma was previously seen on endoscopy. However, total gastrectomy is not without significant morbidity, and many patients are reluctant to follow this recommendation. Attempts at endoscopic surveillance using standard white-light endoscopy with random biopsy protocols have proved inadequate since the overlying mucosa tends to be normal. EUS is unlikely to be helpful as early HDGC foci are very small. Much better results have been obtained using chromoendoscopy with congo red and methylene blue staining. Unfortunately, due to concerns over the potential carcinogenicity of congo red, this is not a current option at our institution. New endoscopic techniques such as confocal microendoscopy, narrow-band imaging and immunophotodiagnostics hold future promise but have not yet been studied in diffuse gastric cancer.
CONCLUSION: Currently available endoscopic strategies are inadequate. More research is needed to confirm the safety of congo red and to test new endoscopic techniques in order to offer reliable surveillance to patients refusing gastrectomy.