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Hereditary gastric cancer

Familiäres Magenkarzinom

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Abstract

In 1998, Guilford et al. identified the hereditary diffuse gastric cancer (HDGC) syndrome, caused by germline alterations at the CDH1 (E-cadherin) gene. To date, 141 probands harboring more than 100 different germline CDH1 alterations, mainly point mutations and large deletions, have been described. In mutation-positive individuals prophylactic total gastrectomy is recommended. The systematic histological study of prophylactic gastrectomies shows intramucosal signet-ring cell carcinoma and pre-invasive lesions including in situ signet ring carcinoma with pagetoid spread of signet ring cells. In 2011, a new hereditary gastric cancer syndrome was identified: gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). GAPPS is a unique gastric polyposis syndrome with a significant risk of gastric adenocarcinoma, characterized by the autosomal dominant transmission of fundic gland polyposis, with areas of dysplasia or intestinal-type GC, restricted to the proximal stomach, with no evidence of colorectal or duodenal polyposis or other heritable gastrointestinal cancer syndromes.

Zusammenfassung

Guilford et al. identifizierten 1998 das Syndrom des familiären diffusen Magenkarzinoms („hereditary diffuse gastric cancer“, HDGC), das durch Keimbahnmutationen im CDH1(E-Cadherin)-Gen verursacht wird. Bisher wurden bei 141 Probanden mehr als 100 verschiedene CDH1-Keimbahnmutationen beschrieben, hauptsächlich Punktmutationen und große Deletionen. Bei Mutationsträgern wird die prophylaktische totale Gastrektomie empfohlen. In der systematischen histologischen Untersuchung bei prophylaktischer Gastrektomie zeigen sich intramukosale Siegelringzellkarzinome und präinvasive Läsionen einschließlich In-situ-Siegelringkarzinomen mit pagetoider Ausbreitung der Siegelringzellen. Ein neues Magenkarzinomsyndrom wurde 2011 identifiziert: das Adenokarzinom und die proximale Polypose des Magens („gastric adenocarcinoma and proximal polyposis of the stomach“, GAPPS). Das GAPPS-Syndrom ist ein eigenes Magenpolyposissyndrom mit erheblichem Risiko für ein Adenokarzinom des Magens bei autosomal-dominanter Übertragung. Die Fundusdrüsenpolypose ist gekennzeichnet durch auf den proximalen Teil des Magens begrenzte Bereich mit Dysplasie oder Magenkarzinom ohne Anhalt für eine kolorektale oder duodenale Polypose oder andere erbliche gastrointestinale Karzinomsyndrome.

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Conflict of interest

The author states that there are no conflicts of interest. The supplement that this article is part of is not sponsored by industry.

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Authors and Affiliations

  1. Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Rua Dr Roberto Frias S/N, 4200-465, Porto, Portugal

    F. Carneiro MD, PhD

  2. Medical Faculty, University of Porto, Porto, Portugal

    F. Carneiro MD, PhD

  3. Department of Pathology, Centro Hospitalar de São João, Porto, Portugal

    F. Carneiro MD, PhD

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Correspondence to F. Carneiro MD, PhD.

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Carneiro, F. Hereditary gastric cancer. Pathologe 33 (Suppl 2), 231–234 (2012). https://doi.org/10.1007/s00292-012-1677-6

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