Large intra- and inter-individual variability of genes expression levels limits potential predictive value of molecular diagnosis of dysplasia in Barrett's esophagus.
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 esophagus with high-grade dysplasia, only a decrease in S100A2 mRNA levels was statistically significant (P<0.05). However, there was considerable variation among individuals and significant overlapping of ranges. Furthermore, detailed, comparative analysis of serial samples from Barrett's mucosa and normal squamous epithelium shows large intra-individual variability of gene expression levels. In conclusion, expression of this set of ten genes cannot be used as a molecular marker aiding histological examination of dysplasia in Barrett's esophagus. Significant inter- and intra-patient variations of gene expression levels makes use of the selected genes impractical.
Hennig
Ewa E
EE
Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
Mikula
Michal
M
Orlowska
Janina
J
Jarosz
Dorota
D
Bielasik
Andrzej
A
Regula
Jaroslaw
J
Ostrowski
Jerzy
J
D001471:Barrett Esophagus / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002630:Chemotactic Factors / Q000235:genetics; D018450:Disease Progression; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D004945:Esophagoscopy; D004947:Esophagus / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D005819:Genetic Markers; D005820:Genetic Testing / Q000379:methods; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D025202:Molecular Diagnostic Techniques; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009418:S100 Proteins / Q000235:genetics; D012720:Severity of Illness Index
D002630:Chemotactic Factors; D005819:Genetic Markers; D012333:RNA, Messenger; D009418:S100 Proteins; C098997:S100A2 protein, human