J Mol Med (2008) 86:233–242 DOI 10.1007/s00109-007-0271-5
ORIGINAL ARTICLE
Large intra- and inter-individual variability of genes expression levels limits potential predictive value of molecular diagnosis of dysplasia in Barrett’s esophagus Ewa E. Hennig & Michal Mikula & Janina Orlowska & Dorota Jarosz & Andrzej Bielasik & Jaroslaw Regula & Jerzy Ostrowski
Received: 30 July 2007 / Revised: 3 September 2007 / Accepted: 19 September 2007 / Published online: 19 October 2007 # Springer-Verlag 2007
Abstract Barrett’s esophagus represents a well-defined precursor lesion of esophageal adenocarcinoma, although only a subset of patients with these lesions advances to invasive cancer. Currently, reliable markers predicting neoplastic progression in Barrett’s esophagus are lacking. The only clinically useful risk factor is the presence of dysplasia in Barrett’s epithelium, but its use as a prognostic marker of disease progression has several significant limitations. Thus, identification of biomarkers of potential prognostic value in dysplasia development in Barrett’s esophagus is highly important. The aim of the study was to determine if expression levels of selected genes support histologic diagnosis of dysplastic changes in Barrett’s esophagus. Upon rigorous sampling and independent histopathologic examination of endoscopic specimens by two experienced gastrointestinal pathologists, 56 patients with Barrett’s esophagus (16 negative for dysplasia, 15 with indefinite, 21 with low-grade, and 4 with high-grade dysplasia) were selected for molecular analysis. The relative mRNA levels of ten selected genes were estimated by quantitative real-time polymerase chain reaction (PCR) analysis. Although expression of nine genes showed trends toward down- or upregulation during progression from Barrett’s esophagus without dysplasia to Barrett’s E. E. Hennig : M. Mikula : J. Orlowska : D. Jarosz : A. Bielasik : J. Regula : J. Ostrowski Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland J. Ostrowski (*) Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education in Cancer Center, Roentgena 5, 02–781 Warsaw, Poland e-mail:
[email protected]
EWA E. HENNIG graduated at the Warsaw University in biology and received her Ph.D. in Toxicology from University School of Medicine in Warsaw, Poland. She is presently an Associate Professor of Biomedical Science at the Department of Gastroenterology, Medical Center for Postgraduate Education and Cancer Center in Warsaw. Her main research interests include the application of nanotechnologies to screening for molecular biomarkers of malignancies.
JERZY OSTROWSKI received his Ph.D. and doctor habilitatus degrees in medicine from the Medical Center for Postgraduate Education, Warsaw, where he is presently a Professor of Medicine at the Department of Gastroenterology. He is also a Chief of the Laboratory of Molecular Gastroenterology at Cancer Center. One of his research interests includes the application of integrative genomics to study molecular mechanisms of complex diseases.
esophagus with high-grade dysplasia, only a decrease in S100A2 mRNA levels was statistically significant (P
