Original Article Toponostics of invasive ductal breast carcinoma: combination of spatial protein expression imaging and quantitative proteome signature analysis
Claudia Röwer, Björn Ziems, Anngret Radtke, Oliver Schmitt, Toralf Reimer, Cornelia Koy, Hans-Jürgen Thiesen, Bernd Gerber, Michael O. Glocker
Proteome Center Rostock, University of Rostock, Rostock, Germany. Institute of Immunology, University of Rostock, Rostock, Germany. IndyMed GmbH, Rostock, Germany. Partnerschaft der Fachärzte für Pathologie, Südstadt Clinical Center, Rostock, Germany. Department of Anatomy, University of Rostock, Rostock, Germany. Department of Obstetrics and Gynecology, University of Rostock, Rostock, Germany
Received May 31, 2011; accepted June, 2011; Epub June, 2011, published June, 2011
Abstract: Due to enormous advances in quantitative proteomics and in immunohisto¬chemistry (pathology), the two research areas have now reached the state to be successfully interwoven in order to tackle challenges in toponostics and to open tumor-targeted systems pathology approaches. In this study the differential expressions of candidate proteins nucleophosmin, NDKA/B, osteoinducive factor (mimecan), and pyruvate kinase M2 from a quantitative proteome signature for invasive ductal breast cancer were determined by immunohistochemistry on 53 tissue slices from formalin-fixed and paraffin-embedded tumor and control tissue samples from ten patients and fourteen controls. In addition, 87 images from the Human Protein Atlas representing seven tumor and nine normal breast tissue samples were investigated by computer-assisted semi-quantitative density measurements on nucleophosmin, nucleoside diphosphate kinase A/B (NDKA/B), osteoinducive factor (mimecan), pyruvate kinase M2, glyceraldehyde-3-phosphate dehydro¬genase (GAP-DH), and mimecan (osteoinductive factor). Both IHC data sets match well to each other and support the quantitative proteome analysis data. Determining spatial distribution of signature protein expressions by protein imaging on morphologically intact tissue samples at the sub-cellular level and, hence, keeping all topological information, presents an added value to quantitative proteome data. Such comprehensive data sets are needed for both, pathway analyses and for "next generation clinical diagnostics" approaches. (IJCEP1105007)
Keywords: Breast carcinoma, proteome analysis, proteomics, protein expression signature, mass spectrometry, immunohistochemistry, tissue microarrays, image analysis, toponomics, toponostics
Address all correspondence to: Prof. Dr. Michael O. Glocker Proteome Center Rostock Department for Proteome Research Institute of Immunology Medical Faculty and Natural Science Faculty University of Rostock Schillingallee 69 P.O. Box 100 888 18057 Rostock Germany Tel: +49 - 381 - 494 4930 FAX: +49 - 381 - 494 4932 E-mail: michael.glocker@med.uni-rostock.de