From Cell Biology to Tissue Engineering



From Barrett metaplasia to esophageal adenocarcinoma: the molecular background

Deborah Saraggi1,*, Matteo Fassan1,*, Jan Bornschein2,3, Fabio Farinati4, Stefano Realdon5, Nicola Valeri6 and Massimo Rugge1

1Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padua, Padua, Italy, 2Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany, 3MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge, UK, 4Department of Surgical Oncology and Gastroenterology (DiSCOG), Gastroenterology Unit, University of Padua, Padua, Italy, 5Istituto Oncologico Veneto, IOV-IRCCS, Gastroenterology Unit, Padua, Italy and 6Institute of Cancer Research, London, UK
*Equally contributed

Offprint requests to: Matteo Fassan, MD, PhD, Assistant Professor of Pathology, Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Via Gabelli 61 - 35121 Padua (PD), Italy. e-mail: matteo.fassan@unipd.it

Summary. The molecular landscape of Barrett's esophagus and Barrett-related neoplastic lesions is still far from being completely elucidated. Both in vitro and in vivo studies pinpointed the pathogenetic role of different morphogenic pathways (the para-homeobox, the Notch and the Sonic Hedgehog families in particular) implicated in the acquisition of the metaplastic phenotype of the esophageal mucosa. On the other hand, the most common genetic alterations observed during Barrett's carcinogenesis include disorders of major regulators of the cell cycle, as well as deregulation of the TGF-β/Smad and receptor tyrosine kinases signalling pathways. Recent comprehensive mutational profiling studies identified that the inactivation of the TP53 and of the SMAD4 tumour suppressor genes occurred in a stage-specific manner, confined to (high grade) dysplastic and neoplastic lesions, respectively. The next step will be the correlation of these findings into multidisciplinary diagnostic approaches integrating endoscopy, histology, molecular profiling and liquid biopsies. This will allow the introduction of innovative strategies for secondary prevention of esophageal adenocarcinoma based on biological rationales, and the implementation of potential novel therapeutic targets. Histol Histopathol 31, 25-32 (2016)

Key words: Barrett's esophagus, Molecular pathology, Biomarker, MicroRNA

DOI: 10.14670/HH-11-659