Hereditary Diffuse Gastric Cancer: updated consensus guidelines for clinical management and directions for future research

Rebecca C Fitzgerald (1) , Richard Hardwick (2) , David Huntsman (3) , Fatima Carneiro (4) , Parry Guilford (5) , Vanessa Blair (5) , Daniel Chung (6) , Jeff Norton (7) , Krishnadath Ragunath (8) , J Han van Krieken (9) , Sarah Dwerryhouse (2) , Carlos Caldas (10) , Interntaional Gastric Linkage Consortium (11)

1 MRC Cancer Cell Unit
2 Addenbrooke's Hospital
3 British Columbia Cancer Agency, Vancouver,
4 Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) and Medical Fa
5 University of Otago [Dunedin, Nouvelle-Zélande]
6 GI Cancer Genetics Clinic, Gastrointestinal Unit, Massachusetts General Hospital, Boston
7 Stanford University
8 9Wolfson Digestive Diseases Centre, Queens Medical Centre, Nottingham University Hospitals NHS Trust
9 University Nijmegen Medical Centre, Nijmegen,
10 Cancer Research UK Cambridge Research Institute and Department of Oncology, University of Cambridge
11 Consortium

25-30% of families fulfilling the criteria for Hereditary Diffuse Gastric Cancer have germline mutations of the CDH1 (E-cadherin) gene. In light of new data and advancement of technologies a multidisciplinary workshop was convened to discuss genetic testing, surgery, endoscopy and pathology reporting. The updated recommendations include broadening of CDH1 testing criteria such that: histological confirmation of diffuse gastric criteria is only required for 1 family member; inclusion of individuals with diffuse gastric cancer before the age of 40 yrs without a family history; and inclusion of individuals and families with diagnoses of both diffuse gastric cancer (including one before the age of 50 yrs) and lobular breast cancer. Testing is considered appropriate from the age of consent following counseling and discussion with a multidisciplinary team. In addition to direct sequencing large genomic rearrangements should be sought. Annual mammography and breast MRI from the age of 35 yrs is recommended for women due to the increased risk for lobular breast cancer. In mutation positive individuals prophylactic total gastrectomy at a centre of excellence should be strongly considered. Protocolised endoscopic surveillance in centres with endoscopists and pathologists experienced with these patients is recommended for: those opting not to have gastrectomy, those with mutations of undetermined significance and in those families for whom no germline mutation is yet identified. The systematic histological study of prophylactic gastrectomies almost universally shows pre-invasive lesions including in situ signet ring carcinoma with pagetoid spread of signet ring cells. Expert histopathological confirmation of these early lesions is recommended.

Mots clés: Guidelines; Gastroenterology

Rebecca C Fitzgerald, Richard Hardwick, David Huntsman, Fatima Carneiro, Parry Guilford, et al.. Hereditary Diffuse Gastric Cancer: updated consensus guidelines for clinical management and directions for future research. Journal of Medical Genetics, 2010, 47 (7), pp.436. ⟨10.1136/jmg.2009.074237⟩. ⟨hal-00557381⟩