Evaluation of SOX9, bBMP4, beta-catenin, CERB2 and Kİ67 expressions in barrett's esophagus and esophageal adenocarcinoma

ABSTRACT Evaluation of SOX9, BMP4, Beta-Catenin, CERB2 and KI67 Expressions In Barrett's Esophagus and Esophageal Adenocarcinoma Introduction and Aims: The incidence of esophagus adenocarcinoma is growing in the Western countries. The mortality and morbidity of esophageal adenocarcinoma is high with very limited cure alternatives. Barrett's esophagus is known to be the precursor lesion of esophageal adenocarcinoma. Nevertheless, the progress mechanism of Barrett's esophagus and the malign transformation mechanism of esophageal adenocarcinoma is still elusive. Recent studies focus on aberrant reactivation of embryological signalling pathways such as WNT, HH, BMP and RA. In this study, indicators for WNT, HH and BMP signalling pathways were applied to no dysplasia, low grade dysplasia and high grade dysplasia of Barrett's esophagus and esophageal adenocarcinoma cases. The contribution of these agents to the progress of metaplasia, dysplasia and carcinogenesis was evaluated in order to isolate the pathways and molecules, for devising potential cures of the aferomentioned esophageal diseases. Materials and Methods: In this study, two hundred and fourty two Barrett's esophagus cases diagnosed in between 2010 and 2015 and seventeen esophageal adenocarcinoma cases diagnosed in our department between 2005 and 2015 were included. SOX9, BMP4, Betacatenin, CerbB2, Ki67 indicators were applied to the cases using immunohistochemical methods and the cases were clustered according to the Grade levels, then their expression in Barrett's esophagus and esophageal adenocarcinoma cases were analyzed. Results: Betacatenin and SOX9 have shown significantly lower nuclear immunoreactivity in no dysplasia Barrett's esophagus cases compared to Barrett's esophagus with dysplasia and esophageal adenocarcinoma. BMP4 has shown positive staining in stromal fibroblasts for no dysplasia Barrett's esophagus cases, whereas no staining was observed in Barrett's esophagus with dysplasia and adenocarcinoma groups. CerbB2 expression is observed to be significantly large for Barrett's esophagus with dysplasia and adenocarcinoma cases. Ki67 expression has shown statistically significant increase during the transition from no dysplasia to dysplasia, and the cut-off value is determined to be 30%. Conclusions: In this study, we discovered that Betacatenin and SOX9 do not affect metaplasia progress yet they acts on in dysplastic progression. Contrarily, BMP is affective in metaplasia progress and inactive for dysplasia-carcinoma sequence. CerbB2 is playing a role in advanced stages of dysplasia and esophageal adenocarcinoma. Keywords: Barrett's esophagus, esophageal adenocarcinoma, Betacatenin, SOX9, BMP4, CerbB2, Ki67