title: Chromosomal imbalances in gastric and esophageal adenocarcinoma: specific comparative genomic hybridization-detected abnormalities segregate with junctional adenocarcinomas.
abstract: The incidence of adenocarcinoma arising at the esophagogastric junction (EGJ) is increasing at a rate greater than that for any other form of solid malignancy. Commensurate with this, the incidence of histologically similar tumors arising in the gastric body and antral mucosa is declining. The increased incidence of the proximal group of tumors may reflect, in part, the higher prevalence of Barrett esophagus. These epidemiological features suggest that histologically similar tumors arising at the EGJ and from the distal stomach are different, which may be reflected in the genetic abnormalities that characterize the two groups of tumors. The purpose of this study was to screen genomic DNA from adenocarcinomas of the esophagus and stomach for regions of chromosomal imbalance, using comparative genomic hybridization to determine whether tumors at the EGJ (junctional tumors) have a different profile compared with tumors of the distal stomach. Tumor samples were derived from a series of 48 gastroesophageal adenocarcinomas (20 junctional and 28 distal) that were acquired prospectively from patients undergoing esophagogastrectomy. These tumors are characterized by several regions of chromosomal imbalance with no obvious correlation between most regions of abnormal copy number and tumor type. However, our study shows for the first time cytogenetic abnormalities (5p+ and 18q-) that identify statistically significant differences (P < 0.02 and < 0.05, respectively) between junctional and distal gastric tumors. These differences are gain of 5p (55% [11/20] of junctional tumors vs. 21% [6/28] of distal gastric tumors) and loss of 18q (25% [5/20] cases of junctional tumors vs. 4% [1/28] of distal tumors) segregating with tumors of the EGJ. These abnormalities may distinguish distinct tumor subtypes that are recognized in epidemiological and clinical studies but that are otherwise histologically identical.
authors.affiliation: Department of Molecular and Cellular Pathology, University of Dundee, Tayside University Hospitals Trust, Dundee, United Kingdom.
authors.forename: S C
authors.initials: SC
authors.lastname: Stocks
authors.forename: N
authors.initials: N
authors.lastname: Pratt
authors.forename: M
authors.initials: M
authors.lastname: Sales
authors.forename: D A
authors.initials: DA
authors.lastname: Johnston
authors.forename: A M
authors.initials: AM
authors.lastname: Thompson
authors.forename: F A
authors.initials: FA
authors.lastname: Carey
authors.forename: N M
authors.initials: NM
authors.lastname: Kernohan
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D022981:Allelic Imbalance / Q000235:genetics*; D002869:Chromosome Aberrations / Q000453:epidemiology / Q000235:genetics*; D025063:Chromosome Disorders; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004943:Esophagogastric Junction / Q000473:pathology*; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D015994:Incidence; D009693:Nucleic Acid Hybridization; D009857:Oncogenes / Q000235:genetics; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics*; D014407:Tumor Cells, Cultured