title: Aneuploidy involving chromosome 1 may be an early predictive marker of intestinal type gastric cancer.
abstract: Intestinal type gastric cancer is a significant cause of mortality, therefore a better understanding of its molecular basis is required. We assessed if either aneuploidy or activity of the oncogenic transcription factor nuclear factor kappa B (NF-kappaB), increased incrementally during pre-malignant gastric histological progression and also if they correlated with each other in patient samples, as they are both induced by oxygen free radicals. In a prospective study of 54 (aneuploidy) and 59 (NF-kappaB) consecutive patients, aneuploidy was assessed by interphase fluorescent in situ hybridisation (FISH) for chromosome 1. NF-kappaB was assessed by expression of interleukin-8 (IL-8), and in a subset, by immunohistochemistry (IHC) for active p65. Aneuploidy levels increased incrementally across the histological series. 2.76% of cells with normal histology (95% CI, 2.14-3.38%) showed background levels of aneuploidy, this increased to averages of 3.78% (95% CI, 3.21-4.35%), 5.89% (95% CI, 3.72-8.06%) and 7.29% (95% CI, 4.73-9.85%) of cells from patients with gastritis, Helicobacter pylori positive gastritis and atrophy/intestinal metaplasia (IM) respectively. IL-8 expression was only increased in patients with current H. pylori infection. NF-kappaB analysis showed some increased p65 activity in inflamed tissues. IL-8 expression and aneuploidy level were not linked in individual patients. Aneuploidy levels increased incrementally during histological progression; were significantly elevated at very early stages of neoplastic progression and could well be linked to cancer development and used to assess cancer risk. Reactive oxygen species (ROS) induced in early gastric cancer are presumably responsible for the stepwise accumulation of this particular mutation, i.e. aneuploidy. Hence, aneuploidy measured by fluorescent in situ hybridisation (FISH) coupled to brush cytology, would be worthy of consideration as a predictive marker in gastric cancer and could be clinically useful in pre-malignant disease to stratify patients by their cancer risk.
authors.affiliation: Royal Glamorgan Hospital, Ynysmaerdy, Llantrisant, United Kingdom.
authors.forename: L
authors.initials: L
authors.lastname: Williams
authors.forename: A
authors.initials: A
authors.lastname: Somasekar
authors.forename: D J
authors.initials: DJ
authors.lastname: Davies
authors.forename: J
authors.initials: J
authors.lastname: Cronin
authors.forename: S H
authors.initials: SH
authors.lastname: Doak
authors.forename: R
authors.initials: R
authors.lastname: Alcolado
authors.forename: J G
authors.initials: JG
authors.lastname: Williams
authors.forename: A P
authors.initials: AP
authors.lastname: Griffiths
authors.forename: J N
authors.initials: JN
authors.lastname: Baxter
authors.forename: G J S
authors.initials: GJ
authors.lastname: Jenkins
mesh_terms: D000782:Aneuploidy; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D005756:Gastritis / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species