title: Oxygen supply maps for hypoxic microenvironment visualization in prostate cancer.
abstract: BACKGROUND
  Intratumoral hypoxia plays an important role with regard to tumor biology and susceptibility to radio- and chemotherapy. For further investigation of hypoxia-related changes, areas of certain hypoxia must be reliably detected within cancer tissues. Pimonidazole, a 2-nitroimindazole, accumulates in hypoxic tissue and can be easily visualized using immunohistochemistry.
  
  
  METHODS
  To improve detection of highly hypoxic versus normoxic areas in prostate cancer, immunoreactivity of pimonidazole and a combination of known hypoxia-related proteins was used to create computational oxygen supply maps of prostate cancer. Pimonidazole was intravenously administered before radical prostatectomy in n = 15 patients, using the da Vinci robot-assisted surgical system. Prostatectomy specimens were immediately transferred into buffered formaldehyde, fixed overnight, and completely embedded in paraffin. Pimonidazole accumulation and hypoxia-related protein expression were visualized by immunohistochemistry. Oxygen supply maps were created using the normalized information from pimonidazole and hypoxia-related proteins.
  
  
  RESULTS
  Based on pimonidazole staining and other hypoxia.related proteins (osteopontin, hypoxia-inducible factor 1-alpha, and glucose transporter member 1) oxygen supply maps in prostate cancer were created. Overall, oxygen supply maps consisting of information from all hypoxia-related proteins showed high correlation and mutual information to the golden standard of pimonidazole. Here, we describe an improved computer-based ex vivo model for an accurate detection of oxygen supply in human prostate cancer tissue.
  
  
  CONCLUSIONS
  This platform can be used for precise colocalization of novel candidate hypoxia-related proteins in a representative number of prostate cancer cases, and improve issues of single marker correlations. Furthermore, this study provides a source for further in situ tests and biochemical investigations.
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
authors.forename: Niels J
authors.initials: NJ
authors.lastname: Rupp
authors.affiliation: Department of Computer Science, ETH Zurich, Universitaetstr 6, 8092 Zurich, Switzerland.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schüffler
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhong
authors.affiliation: Institute of Pathology, Cantonal Hospital Winterthur, Brauerstrasse 15, 8401 Winterthur, Switzerland.
authors.forename: Florian
authors.initials: F
authors.lastname: Falkner
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Rechsteiner
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Rüschoff
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Fankhauser
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Drach
authors.affiliation: Department of Urology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
authors.forename: Remo
authors.initials: R
authors.lastname: Largo
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland.
authors.forename: Mathias
authors.initials: M
authors.lastname: Tremp
authors.affiliation: Department of Urology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
authors.forename: Cedric
authors.initials: C
authors.lastname: Poyet
authors.affiliation: Department of Urology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
authors.forename: Tullio
authors.initials: T
authors.lastname: Sulser
authors.affiliation: Institute of Pathology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.affiliation: Department of Computer Science, ETH Zurich, Universitaetstr 6, 8092 Zurich, Switzerland.
authors.forename: Joachim
authors.initials: J
authors.lastname: Buhmann
authors.affiliation: Department of Urology, City Hospital Triemli, Birmensdorferstrasse 497, 8063 Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Müntener
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wild
keywords: Hypoxia; pimonidazole; prostate cancer