TY - JOUR
T1 - Aneuploidy and high expression of p53 and Ki67 is associated with neoplastic progression in Barrett esophagus
AU - Kerkhof, Marjon
AU - Steyerberg, Ewout W.
AU - Kusters, Johannes G.
AU - van Dekken, Herman
AU - van Vuuren, Adriana J.
AU - Kuipers, Ernst J.
AU - Siersema, Peter D.
PY - 2008
Y1 - 2008
N2 - Unless detected at an early stage, esophageal adenocarcinoma (EAC) has a poor prognosis. Changes in cellular DNA content and expression levels of p53 and Ki67 in Barrett esophagus (BE) are associated with the development EAC and might serve as markers to identify EAC at an early stage. The aim of this study was to examine the presence of these three markers in various steps of neoplastic progression in BE towards EAC. Dysplasia was graded in 212 biopsy sets taken during follow-up upper endoscopy in 27 patients in whom ultimately high-grade dysplasia (HGD) or EAC was detected. Ploidy status was determined by flow cytometry, whereas Ki67 and p53 expression were determined by immunohistochemistry. Smoothing splines were used to analyze trends in time. We found an increasing fraction of Ki67 overexpression and, to a lesser extent, abnormal DNA content in biopsies closer to the time-point of detecting HGD/EAC in BE, suggesting the potential value of these biomarkers in identifying patients at increased risk of progression towards HGD/EAC. Accumulation of p53 was seen several years before development of HGD/EAC, and may therefore be an early marker in BE at a stage when dysplasia is not yet detected. A prospective follow-up study is needed to confirm these findings.
AB - Unless detected at an early stage, esophageal adenocarcinoma (EAC) has a poor prognosis. Changes in cellular DNA content and expression levels of p53 and Ki67 in Barrett esophagus (BE) are associated with the development EAC and might serve as markers to identify EAC at an early stage. The aim of this study was to examine the presence of these three markers in various steps of neoplastic progression in BE towards EAC. Dysplasia was graded in 212 biopsy sets taken during follow-up upper endoscopy in 27 patients in whom ultimately high-grade dysplasia (HGD) or EAC was detected. Ploidy status was determined by flow cytometry, whereas Ki67 and p53 expression were determined by immunohistochemistry. Smoothing splines were used to analyze trends in time. We found an increasing fraction of Ki67 overexpression and, to a lesser extent, abnormal DNA content in biopsies closer to the time-point of detecting HGD/EAC in BE, suggesting the potential value of these biomarkers in identifying patients at increased risk of progression towards HGD/EAC. Accumulation of p53 was seen several years before development of HGD/EAC, and may therefore be an early marker in BE at a stage when dysplasia is not yet detected. A prospective follow-up study is needed to confirm these findings.
KW - Aneuploidy
KW - Barrett esophagus
KW - Intestinal metaplasia
KW - Ki67
KW - p53
UR - http://www.scopus.com/inward/record.url?scp=40449137722&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=40449137722&partnerID=8YFLogxK
U2 - 10.3233/CBM-2008-4101
DO - 10.3233/CBM-2008-4101
M3 - Article
C2 - 18334729
AN - SCOPUS:40449137722
SN - 1574-0153
VL - 4
SP - 1
EP - 10
JO - Cancer Biomarkers
JF - Cancer Biomarkers
IS - 1
ER -
