Loss of SRY-box2 (SOX2) expression predicts adverse survival of patients with esophageal adenocarcinoma

摘要: Introduction: Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy with poor survival, which is highly variable amongst patients with comparable conventional prognosticators. Therefore molecular biomarkers are urgently needed to improve survival prediction in these patients. SRY (sex determining region Y)-box 2, also known as SOX2, is a transcription factor involved in embryonal development of the gastrointestinal tract as well as in carcinogenesis. Here we aimed to test whether SOX2 expression is associated with survival in patients with EAC.Methods: SOX2 was studied by immunohistochemistry in patients who had undergone potentially curative esophagectomy for adenocarcinoma. Protein expression of SOX2 was evaluated using tissue micro arrays from resection specimens and the results were analyzed in relation to the clinical data by Cox regression analysis. SOX2 was evaluated in two independent EAC cohorts (Rotterdam cohort and multicenter UK cohort). Results: Loss of SOX2 expression was independently predictive for adverse overall survival (OS) in the multivariate analysis adjusted for known factors influencing survival, in Rotterdam as well as in the UK cohort (Rotterdam cohort: HR= 1.42, 95% CI 1.07-1.89, p= 0.016; UK cohort: HR= 1.54, 95% CI 1.08-2.19, p= 0.017). When combined with clinico-pathological staging, SOX2 segregated patients into prognostic groups in pT1/2 tumors (p= 0.01) and nodal-negative EAC (p= 0.038), with incremental adverse effect on OS for stage I EAC with SOX2 loss (HR= 3.18, 95% CI 1.18-8.56, p= 0.022). Conclusions: We identified SOX2 as an independent prognostic factor …