title: Correlation between Faecal Tumour M2 Pyruvate Kinase and Colonoscopy for the Detection of Adenomatous Neoplasia in a Secondary Care Cohort.
abstract: OBJECTIVE
  Colorectal cancer screening programmes that target detection and excision of adenomatous colonic polyps have been shown to reduce colorectal cancer related mortality. Many screening programmes include an initial faecal occult blood test (FOBt) prior to colonoscopy. To refine the selection of patients for colonoscopy other faecal-based diagnostic tools have been proposed, including tumour M2-pyruvate kinase (tM2-PK). To determine whether tM2-PK quantification may have a role in diverse settings we have assessed the assay in a cohort of patients derived from both the England bowel cancer screening programme (BCSP) and symptomatic individuals presenting to secondary care.
  
  
  METHODS
  Patients undergoing colonoscopy provided faecal samples prior to bowel preparation. Faecal tM2-PK concentrations were measured by ELISA. Sensitivity, specificity, positive predictive value, negative predictive value and ROC analyses were calculated.
  
  
  RESULTS
  Ninety-six patients returned faecal samples: 50 of these with adenomas and 7 with cancer. Median age was 68. Median faecal tM2-PK concentration was 3.8 U/mL for individuals without neoplastic findings at colonoscopy, 7.7 U/mL in those with adenomas and 24.4 U/mL in subjects with colorectal cancer (both, p=0.01). ROC analysis demonstrated an AUROC of 0.66 (sensitivity 72.4%, specificity 48.7%, positive predictive value 67.7%, negative predictive value 36.7%). Amongst BCSP patients with a prior positive FOBt faecal tM2-PK was more abundant (median 6.4 U/mL, p=0.03) and its diagnostic accuracy was greater (AUROC 0.82).
  
  
  CONCLUSIONS
  Our findings confirm that faecal tM2-PK ELISA may have utility as an adjunct to FOBt in a screening context, but do not support its use in symptomatic patients.
authors.affiliation: Unit of Gastroenterology Research, Dept of Molecular and Cellular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. abond@liverpool.ac.uk.
authors.forename: Ashley D
authors.initials: AD
authors.lastname: Bond
authors.affiliation: Unit of Gastroenterology Research, Dept of Molecular and Cellular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Burkitt
authors.affiliation: Unit of Gastroenterology Research, Dept of Molecular and Cellular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: David
authors.initials: D
authors.lastname: Sawbridge
authors.affiliation: Molecular Gastroenterology Research Group, Department of Oncology; Insigneo Institute for in silico Medicine, University of Sheffield, Sheffield, UK.
authors.forename: Bernard M
authors.initials: BM
authors.lastname: Corfe
authors.affiliation: Unit of Gastroenterology Research, Dept of Molecular and Cellular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Chris S
authors.initials: CS
authors.lastname: Probert
mesh_terms: D018256:Adenomatous Polyps / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology; D003111:Colonic Polyps / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology; D003113:Colonoscopy; D055088:Early Detection of Cancer / Q000379:methods*; D004739:England; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D011770:Pyruvate Kinase / Q000032:analysis*; D012372:ROC Curve; D015203:Reproducibility of Results; D063127:Secondary Health Care; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D011770:Pyruvate Kinase