Article Text

Download PDFPDF
Over-expression of phosphorylated mammalian target of rapamycin is associated with poor survival in oesophageal adenocarcinoma: a tissue microarray study
  1. Margriet J D Prins1,
  2. Roy J J Verhage1,
  3. Jelle P Ruurda1,
  4. Fiebo J W ten Kate2,
  5. Richard van Hillegersberg1
  1. 1Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
  1. Correspondence to Professor Richard van Hillegersberg, Department of Surgery, University Medical Center Utrecht, PO Box 85500, Utrecht 3508 GA, The Netherlands; R.vanHillegersberg{at}umcutrecht.nl

Abstract

Background Protein kinase mammalian target of rapamycin (mTOR) is an important downstream effector of the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway. In several tumour types, phosphorylated mTOR (p-mTOR) over-expression is an independent prognostic marker for poor survival. However, p-mTOR expression has not been assessed in oesophageal adenocarcinoma (OAC).

Materials and methods Tumour cores of 154 patients with OAC were included in a tissue microarray (TMA). Scoring criteria were based on p-mTOR staining intensity.

Results 147 (95.5%) patients were available for immunohistochemical evaluation. Over-expression of p-mTOR was detected in 29 (19.7%) tumours, whereas 118 (80.3%) patients showed negative expression. Over-expression was significantly associated with poor overall survival in univariate analysis (HR 1.648; 95% CI 1.019 to 2.664; p=0.042). Median survival was 21.2 months in patients with p-mTOR over-expression and 29.0 in the negative p-mTOR group (p=0.040). In addition, a trend towards p-mTOR over-expression and vasoinvasive growth was seen (p=0.057). In multivariate analysis, including clinical and pathological variables (p<0.10), only T-stage (HR 2.795; 95% CI 1.343 to 5.813; p=0.006) and differentiation grade (HR 2.198; 95% CI 1.353 to 3.570; p=0.001) were independent prognostic markers of poor survival.

Conclusion p-mTOR over-expression was detected in 19.7% of patients with OAC and was associated with poor overall survival.

  • Gastroenterology
  • Molecular Pathology
  • Molecular Oncology
  • Micro Array

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.