title: Expression of KOC, S100P, mesothelin and MUC1 in pancreatico-biliary adenocarcinomas: development and utility of a potential diagnostic immunohistochemistry panel.
abstract: BACKGROUND
  Pancreatico-biliary adenocarcinomas (PBA) have a poor prognosis. Diagnosis is usually achieved by imaging and/or endoscopy with confirmatory cytology. Cytological interpretation can be difficult especially in the setting of chronic pancreatitis/cholangitis. Immunohistochemistry (IHC) biomarkers could act as an adjunct to cytology to improve the diagnosis. Thus, we performed a meta-analysis and selected KOC, S100P, mesothelin and MUC1 for further validation in PBA resection specimens.
  
  
  METHODS
  Tissue microarrays containing tumour and normal cores in a ratio of 3:2, from 99 surgically resected PBA patients, were used for IHC. IHC was performed on an automated platform using antibodies against KOC, S100P, mesothelin and MUC1. Tissue cores were scored for staining intensity and proportion of tissue stained using a Histoscore method (range, 0-300). Sensitivity and specificity for individual biomarkers, as well as biomarker panels, were determined with different cut-offs for positivity and compared by summary receiver operating characteristic (ROC) curve.
  
  
  RESULTS
  The expression of all four biomarkers was high in PBA versus normal ducts, with a mean Histoscore of 150 vs. 0.4 for KOC, 165 vs. 0.3 for S100P, 115 vs. 0.5 for mesothelin and 200 vs. 14 for MUC1 (p < .0001 for all comparisons). Five cut-offs were carefully chosen for sensitivity/specificity analysis. Four of these cut-offs, namely 5%, 10% or 20% positive cells and Histoscore 20 were identified using ROC curve analysis and the fifth cut-off was moderate-strong staining intensity. Using 20% positive cells as a cut-off achieved higher sensitivity/specificity values: KOC 84%/100%; S100P 83%/100%; mesothelin 88%/92%; and MUC1 89%/63%. Analysis of a panel of KOC, S100P and mesothelin achieved 100% sensitivity and 99% specificity if at least 2 biomarkers were positive for 10% cut-off; and 100% sensitivity and specificity for 20% cut-off.
  
  
  CONCLUSIONS
  A biomarker panel of KOC, S100P and mesothelin with at least 2 biomarkers positive was found to be an optimum panel with both 10% and 20% cut-offs in resection specimens from patients with PBA.
authors: Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden G61 1QH, UK.
authors: Asif
authors: A
authors: Ali
authors: Pathology Laboratory, Forth Valley Royal Hospital, Stirling Road, Larbert FK5 4WR, UK.
authors: Victoria
authors: V
authors: Brown
authors: West of Scotland Pancreatic Unit and Glasgow Royal Infirmary, Alexandra Parade, Glasgow G31 2ER, UK.
authors: Simon
authors: S
authors: Denley
authors: West of Scotland Pancreatic Unit and Glasgow Royal Infirmary, Alexandra Parade, Glasgow G31 2ER, UK.
authors: Nigel B
authors: NB
authors: Jamieson
authors: Beatson Institute for Cancer Research, Glasgow G61 1BD, UK.
authors: Jennifer P
authors: JP
authors: Morton
authors: Beatson Institute for Cancer Research, Glasgow G61 1BD, UK.
authors: Colin
authors: C
authors: Nixon
authors: Medical Oncology, Beatson West of Scotland Cancer Centre, Glasgow G12 0YN, UK.
authors: Janet S
authors: JS
authors: Graham
authors: Beatson Institute for Cancer Research, Glasgow G61 1BD, UK.
authors: Owen J
authors: OJ
authors: Sansom
authors: West of Scotland Pancreatic Unit and Glasgow Royal Infirmary, Alexandra Parade, Glasgow G31 2ER, UK.
authors: C Ross
authors: CR
authors: Carter
authors: West of Scotland Pancreatic Unit and Glasgow Royal Infirmary, Alexandra Parade, Glasgow G31 2ER, UK.
authors: Colin J
authors: CJ
authors: McKay
authors: Department of Pathology, Southern General Hospital, Greater Glasgow & Clyde NHS, Glasgow G51 4TF, UK.
authors: Fraser R
authors: FR
authors: Duthie
authors: Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden G61 1QH, UK ; Department of Pathology, Southern General Hospital, Greater Glasgow & Clyde NHS, Glasgow G51 4TF, UK.
authors: Karin A
authors: KA
authors: Oien
keywords: Biomarkers; Diagnosis; Immunohistochemistry; Pancreatic cancer