title: Role of pathology in the identification of hereditary diffuse gastric cancer: report of a Portuguese family.
abstract: Mutations in E-cadherin gene are the underlying genetic defect in approximately one-third of the hereditary diffuse gastric cancer (HDGC) families described to date. Positive family history of diffuse gastric cancer and early age of onset of gastric tumours are the clinical criteria currently used to qualify for HDGC. In the present study, we describe a Portuguese family with HDGC that was selected for CDH1 mutation screening after histological observation of the gastrectomy specimen of one member, who died at the age of 23 years from widely invasive diffuse gastric carcinoma. The detection in the surgical specimen of tiny foci of intramucosal diffuse carcinoma as well as in situ carcinoma lesions and pagetoid spread of signet ring cells raised the hypothesis of HDGC, which was confirmed by pedigree analysis of the family and detection of CDH1 germline mutation. We conclude that there are morphological hints that may help in the identification of HDGC.
authors.affiliation: Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Rua Dr Roberto Frias s/n, 4200-465 , Porto, Portugal.
authors.forename: Carla
authors.initials: C
authors.lastname: Oliveira
authors.forename: Herculano
authors.initials: H
authors.lastname: Moreira
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
authors.forename: Manuel Cardoso
authors.initials: MC
authors.lastname: de Oliveira
authors.forename: Fátima
authors.initials: F
authors.lastname: Carneiro
mesh_terms: D000328:Adult; D001706:Biopsy; D015820:Cadherins / Q000235:genetics; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000473:pathology / Q000601:surgery; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D005260:Female; D005756:Gastritis / Q000150:complications; D006580:Genetic Carrier Screening; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis; D010375:Pedigree; D011174:Portugal; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery
chemical_list: D015820:Cadherins
references.citation: Oncogene. 2002 Jul 11;21(30):4646-62
references.pmid: 12096341
references.citation: Nature. 1998 Mar 26;392(6674):402-5
references.pmid: 9537325
references.citation: N Engl J Med. 2001 Jun 21;344(25):1904-9
references.pmid: 11419427
references.citation: J Med Genet. 1999 Dec;36(12):873-80
references.pmid: 10593993
references.citation: Hum Mol Genet. 2003 Mar 1;12(5):575-82
references.pmid: 12588804
references.citation: J Med Genet. 2004 Jul;41(7):508-17
references.pmid: 15235021
references.citation: Hered Cancer Clin Pract. 2004 May 15;2(2):51-64
references.pmid: 20233471
references.citation: J Pathol. 2004 Jun;203(2):681-7
references.pmid: 15141383
references.citation: Gut. 2004 Jun;53(6):775-8
references.pmid: 15138199
references.citation: Gut. 2004 Jun;53(6):814-20
references.pmid: 15138207
references.citation: Gastroenterology. 2001 Dec;121(6):1348-53
references.pmid: 11729114
references.citation: Eur J Cancer. 2004 Aug;40(12 ):1897-903
references.pmid: 15288293