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Original Article |
1 Department of Surgery, Academic Medical Center at the University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands
2 Department of Pathology, Academic Medical Center at the University of Amsterdam, Amsterdam, The Netherlands
3 Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
4 Department of Medical Oncology, Academic Medical Center at the University of Amsterdam, Amsterdam, The Netherlands
Correspondence: Address correspondence and reprint requests to: S. M. Lagarde, E-mail: S.M.Lagarde{at}amc.uva.nl
Objective: This review describes genetic and molecular changes related to adenocarcinoma of the esophagus and gastroesophageal junction (GEJ) with emphasis on prognostic value and possibilities for targeted therapy in clinical setting.
Summary background data: Adenocarcinoma of the esophagus or GEJ is an aggressive disease with early lymphatic and hematogenous dissemination. Molecular pathology has revealed many molecular mechanisms of disease progression, which are related to prognosis. Some of these factors can be seen as prognostic factors per se. Better knowledge of molecular bases may lead to new paradigms, improved prognostication, early diagnosis and individually tailored therapeutic options.
Methods: A review of recent English literature (1990–October 2005) concerning esophageal adenocarcinoma was performed. This review focuses on genetic and molecular changes as prognosticators of adenocarcinoma of the esophagus and GEJ.
Results: A bewildering number of biomarkers have been described. Many genes and molecules have prognostic impact (cyclin D1, EGFR, Her-2/Neu, APC, TGF-ß, Endoglin, CTGF, P53, Bcl-2, NF-
B, Cox-2, E-cadherin, ß-catenin, uPA, MMP-1,3,7,9, TIMP, TH1/TH2 balance, CRP, PTHrP).
Conclusions: Adenocarcinomas of the esophagus and GEJ show multiple genetic alterations, which indicate that progression of cancer is a multistep complex process with many different alterations. Presumably, it is not one molecular factor that can predict the biological behavior of this cancer. The combination of diverse genetic alterations may better predict prognosis. In future, gene expression analysis with microarrays may reveal important prognostic information and the discovery of new genes and molecules associated with tumor progression and dissemination will enhance prognostication and offers adjuvant therapeutic options.
Abbreviations: APC, Adenomatous polyposis coli • bp, Base pair • CAM, Cell adhesion molecules • COX-2, Cyclooxygenase-2 • CRP, C-reactive protein • CTGF, Connective tissue growth factor • ECM, Extracellular matrix • EGF, Epidermal growth factor • EGFR, Epidermal growth factor receptor • GEJ, Gastroesophageal junction • GERD, Gastroesophageal reflux disease • HGD, High grade dysplasia • LOH, Loss of heterozygosity • MMPs, Matrix metalloproteinases • NF-B, Nuclear factor B • PCNA, Proliferating cell nuclear antigen • PTHrP, Parathyroid hormone-related peptide • Rb, Retinoblastoma protein • TGF-
, Transforming growth factor • TGF-ß, Transforming growth factor ß • TIMP, Tissue inhibitor of metalloproteinases • uPA, Urokinase-type plasminogen activator • VEGF, Vascular endothelial growth factor
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