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Genetic and histological subtypes of gastric cancer reviewed, particularly emphasising on microsatellite instability and E-cadherin gene mutation
Affiliations- Department of Pathology, Pomeranian Medical University, Szczecin, Poland
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Abstract
Almost one million new cases of gastric cancer (GC) were estimated globally in 2012, (i.e. 952,000, representing 6.8% of the total cancer burden), making it the fifth most common malignancy in the world. GC represents a biologically and genetically diverse group of tumours with multifactorial aetiologies; both environmental and genetic. The vast majority of GCs are adenocarcinomas, which can be further subdivided into intestinal and diffuse histological subtypes according to the Lauren classification published in 1965. The molecular classification of GC according to the Cancer Genome Atlas (TCGA) divides GC into four subtypes: tumours positive for the EBV virus (9%), microsatellite unstable tumours (22%), genomically stable tumours (20%) and tumours with chromosomal instability (CIN) at 50%. Most GCs are sporadic by nature, where approximately 10% appear to possess a familial predisposition of which around half can be attributed to hereditary germline mutations i.e. those of the E-cadherin (CDH1) or mismatch repair (MMR) genes. Histopathological characteristics of the tumour type and analysis of potential genetic changes have substantial clinical significance, as they determine the choice of treatment. In this review, we consider the molecular pathogenesis, phenotype and testing of GC placing particular emphasis on microsatellite instability (MSI) and the CDH1 mutation.
Abstract
Almost one million new cases of gastric cancer (GC) were estimated globally in 2012, (i.e. 952,000, representing 6.8% of the total cancer burden), making it the fifth most common malignancy in the world. GC represents a biologically and genetically diverse group of tumours with multifactorial aetiologies; both environmental and genetic. The vast majority of GCs are adenocarcinomas, which can be further subdivided into intestinal and diffuse histological subtypes according to the Lauren classification published in 1965. The molecular classification of GC according to the Cancer Genome Atlas (TCGA) divides GC into four subtypes: tumours positive for the EBV virus (9%), microsatellite unstable tumours (22%), genomically stable tumours (20%) and tumours with chromosomal instability (CIN) at 50%. Most GCs are sporadic by nature, where approximately 10% appear to possess a familial predisposition of which around half can be attributed to hereditary germline mutations i.e. those of the E-cadherin (CDH1) or mismatch repair (MMR) genes. Histopathological characteristics of the tumour type and analysis of potential genetic changes have substantial clinical significance, as they determine the choice of treatment. In this review, we consider the molecular pathogenesis, phenotype and testing of GC placing particular emphasis on microsatellite instability (MSI) and the CDH1 mutation.
Keywords
gastric cancer, histopathological classification, microsatellite instability, E-cadherin gene mutation
About this articleTitle
Genetic and histological subtypes of gastric cancer reviewed, particularly emphasising on microsatellite instability and E-cadherin gene mutation
Journal
Nowotwory. Journal of Oncology
Issue
Article type
Review paper
Pages
193-200
Published online
2017-12-12
Page views
565
Article views/downloads
1033
DOI
Bibliographic record
Nowotwory. Journal of Oncology 2017;67(3):193-200.
Keywords
gastric cancer
histopathological classification
microsatellite instability
E-cadherin gene mutation
Authors
Katarzyna Karpińska
Magdalena Lewandowska
Elżbieta Urasińska