TITLE

INTERPHASE FLUORESCENCE IN SITU HYBRIDISATION (FISH) TO DETECT CHROMOSOMAL ABNORMALITIES IN GASTRIC CANCER PROGRESSION

AUTHOR(S)
Williams, L.; Williams, J.G.; Griffiths, A.P.; Brown, T.; Doak, S.H.; Jenkins, G.J.S.; Parry, E.M.; Parry, J.M.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA50
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Introduction: Gastric cancer is the second commonest fatal cancer worldwide and Helicobacter pylori has been causally linked with cancer progression. Gastric cancer presentation is at the advanced stage, and survival rates are poor. As such, interest in the causative agents and genetic changes responsible for gastric carcinogenesis has increased. Advanced gastric cancer shows widespread chromosomal rearrangement of chromosomes 20, 8, and 17(p53). In addition, chromosome 4 has previously been implicated in Barrett's oesophagus. Aim: To develop FISH to look at chromosomal abnormalities (using 4, 8, 17, 20) in gastric tissue and to correlate the chromosomal abnormalities with histological diagnosis, patient characteristics, H pylori presence and subtype. Methods: Patients were enrolled, gastric biopsies were taken for histology and for PCR to detect H pylori (and Cag A status). Gastric/ oesophageal cytology brushes were taken and FISH performed with centromeric probes 20, 8 and 4, and a locus specific probe for p53 In addition, surgical resections of dysplastic/cancer patients were obtained for FISH analsysis. Results: Oesophageal cells show little chromosomal instability, whilst histologically normal gastric cells do show genetic instability, possibly due to the adverse environment of the stomach. Histologically abnormal gastric cells show significantly more chromosome abnormalities with all probes (p<0.0001) when compared to oesophageal cells or normal gastric cells. This demonstrates the increasing genetic instability in the histological progression of gastric cancer. Specifically, p53 gene deletion, chromosome 8 and 4 amplifications and chromosome 20 instability is detected In the surgically resected specimens, a range of histological subtypes were noted (normal, intestinal metaplasia, dysplasia, adenocarcinoma). The same chromosomal abnormalities seen in the premalignant cells (above), were seen in these cancer cells, but the incidence of these abnormalities...
ACCESSION #
9747609

 

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