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The prognostic value of TP53 mutations in oesophageal adenocarcinoma: a systematic review and meta-analysis
  1. Oliver M Fisher1,
  2. Sarah J Lord1,2,3,
  3. Dan Falkenback1,4,
  4. Nicholas J Clemons5,6,
  5. Guy D Eslick7,
  6. Reginald V Lord1,8
  1. 1Gastroesophageal Cancer Program, St Vincent's Centre for Applied Medical Research University of New South Wales, Sydney, New South Wales, Australia
  2. 2NHMRC Clinical Trials Centre University of Sydney, Sydney, New South Wales, Australia
  3. 3Department of Epidemiology and Medical Statistics, School of Medicine, University of Notre Dame, Sydney, New South Wales, Australia
  4. 4Department of Surgery, Lund University Hospital (Skåne University Hospital) and Lund University, Lund, Sweden
  5. 5Cancer Biology and Surgical Oncology Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  6. 6Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
  7. 7The Whiteley-Martin Research Centre, Discipline of Surgery, The University of Sydney, Sydney, New South Wales, Australia
  8. 8Department of Surgery, School of Medicine, University of Notre Dame, Sydney, New South Wales, Australia
  1. Correspondence to Dr Oliver M Fisher, Gastroesophageal Cancer Research Group, St Vincent's Centre for Applied Medical Research, 405 Liverpool Street, Sydney NSW 2010, Australia; ofisher{at}gmx.ch

Abstract

Objective To clarify the prognostic role of tumour protein 53 (TP53) mutations in patients with oesophageal adenocarcinoma (OAC) as there is a need for biomarkers that assist in guiding management for patients with OAC.

Design A systematic review was conducted using MEDLINE, Embase, PubMed and Current Contents Connect to identify studies published between January 1990 and February 2015 of oesophageal cancer populations (with OAC diagnoses >50% of cases) that measured tumoural TP53 status and reported hazard ratios (HR), or adequate data for estimation of HR for survival for TP53-defined subgroups. Risk of bias for HR estimates was assessed using prespecified criteria for the appraisal of relevant domains as defined by the Cochrane Prognosis Methods Group including adherence to Grading of Recommendations, Assessment, Development and Evaluation and REporting recommendations for tumor MARKer prognostic studies guidelines, as well as assay method used (direct TP53 mutation assessment vs immunohistochemistry) and adjustment for standard prognostic factors. A pooled HR and 95% CI were calculated using a random-effects model.

Results Sixteen eligible studies (11 with OAC only and 5 mixed histology cohorts) including 888 patients were identified. TP53 mutations were associated with reduced survival (HR 1.48, 95% CI 1.16 to 1.90, I2=33%). A greater prognostic effect was observed in a sensitivity analysis of those studies that reported survival for OAC-only cohorts and were assessed at low risk of bias (HR 2.11, 95% CI 1.35 to 3.31, I2=0%).

Conclusions Patients with OAC and TP53 gene mutations have reduced overall survival compared with patients without these mutations, and this effect is independent of tumour stage.

  • OESOPHAGEAL CANCER
  • META-ANALYSIS

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

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