Gastric Cancer

Abstract

Gastric carcinoma is a malignant epithelial tumour of the stomach mucosa. Its aetiology is multifactorial. Gastric cancer can be divided into two variants, each of which accounts for half of the cases. Intestinal‐type carcinomas, the predominant type of tumour in high‐risk areas, have a glandular pattern and are usually accompanied by papillary formation or solid components. By contrast, the so‐called diffuse‐type tumours include signet‐ring cell carcinomas and anaplastic adenocarcinomas whose small and fairly uniform cells spread individually. Genetic alterations in multiple oncogenes, tumour suppressor genes and deoxyribonucleic acid repair genes have been identified. Germline mutations in the cell adhesion molecule E‐CADHERIN are the molecular genetic cause for a hereditary diffuse‐type gastric cancer syndrome. As exemplified by a novel successful targeted therapy against overexpressed HER2, a greater understanding of the biology of gastric cancer may improve treatment selection and overall outcome of individual patients.

Key Concepts:

  • Gastric cancer is among the most frequent causes of cancer death in the world.

  • Genetic alterations for the two subtypes of gastric cancer, intestinal and diffuse type, are different.

  • The declining incidence of gastric cancer is mainly due to the decline of the intestinal type.

  • Infection with Helicobacter pylori is the strongest singular risk factor for cancers of the stomach.

  • Germline mutations in the E‐cadherin gene are associated with a hereditary gastric cancer syndrome.

  • A novel targeted therapy against overexpressed HER2 has shown clinical benefit.

Keywords: gastric cancer; E‐cadherin; oncogene; tumour suppressor gene; molecular pathology; cell adhesion

Figure 1.

Histology of gastric cancer. (a) and (b) Diffuse type: tumour cells (in this example, signet ring cells) infiltrate the surrounding mesenchyme as single cells. (c) and (d) Intestinal type: tumour cells show gland formation. Magnification: (a) and (c) ×100; (b) and (d) ×200.

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Web Links

Adenomatosis polyposis coli (APC); Locus ID: 324. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=324

Adenomatosis polyposis coli (APC); MIM number: 175100. OMIM: http://www.ncbi.nlm.nih.gov/omim?term=175100

Cadherin 1, type 1, E‐cadherin (epithelial) (CDH1); Locus ID: 999. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=999

Cadherin 1, type 1, E‐cadherin (epithelial) (CDH1); MIM number: 192090. OMIM: http://www.ncbi.nlm.nih.gov/omim?term=192090

Met proto‐oncogene (hepatocyte growth factor receptor) (MET); Locus ID: 4233. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=4233

Met proto‐oncogene (hepatocyte growth factor receptor) (MET); MIM number: 164860. OMIM: http://www.ncbi.nlm.nih.gov/omim?term=164860

Tumor protein p53 (Li–Fraumeni syndrome) (TP53); Locus ID: 7157. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=7157

Tumor protein p53 (Li–Fraumeni syndrome) (TP53); MIM number: 191170. OMIM: http://www.ncbi.nlm.nih.gov/omim?term=191170

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Becker, Karl‐Friedrich, and Keller, Gisela(Oct 2010) Gastric Cancer. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006056.pub2]