Detection of genetic changes in Barrett's adenocarcirioma and Barrett's esophagus by DNA in situ hybridization and immunohistochemistry

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Abstract
We have investigated the occurrence of chromosomal DNA and cell cycle-related protein changes in Barrett's epithelium and adenocarcinoma. The presence of numerical chromosomal aberrations was studied by applying nonisotopic in situ hybridization (ISH) with (peri-)centromeric DNA probes, specific for chromosomes 7, 8, 17, and Y, to routinely processed tissue sections of five cases (4 male, 1 female) of Barrett's adenocarcinoma and adjacent Barrett's epithelium. Cell cycle-related protein expression was studied by immunohistochemistry (IHC) for p53 protein and the Ki-67 antigen (Mib-1) in subsequent sections. P53 protein overexpression was found in 3 of the 5 tumors. Overrepresentation of chromosome 8 and loss of chromosome 17 were found in 2 adenocarcinomas, both also negative for p53 protein overexpression. Y-loss, mostly clonal, was detected in 3 of the 4 male adenocarcinomas and 2 cases of adjacent Barrett's epithelium. One tumor had both areas of overrepresentation and loss of the Y chromosome. All Barrett's adenocarcinomas appeared to contain aneuploid cell populations. No relation was found between cell proliferation characteristics and chromosomal aberrations. We conclude that ISH with chromosome specific DNA probes can be applied for the assessment of potentially important numerical chromosome changes in Barrett's esophagus. Further, the combination of IHC and ISH is useful for evaluation of specific genetic events.