Research Papers: Pathology:
TGF-ß isoforms in cancer: Immunohistochemical expression and Smad-pathway-activity-analysis in thirteen major tumor types with a critical appraisal of antibody specificity and immunohistochemistry assay validity
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Markus J. Riemenschneider1,2, Maria Hirblinger1,2, Arabel Vollmann-Zwerenz2,3, Peter Hau2,3, Martin A. Proescholdt2,4, Frank Jaschinski5, Tanja Rothhammer-Hampl1,5, Katja Wosikowski5, Michel Janicot5 and Eugen Leo5
1 Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany
2 Wilhelm Sander Neuro-Oncology Unit, Regensburg University Hospital, Regensburg, Germany
3 Department of Neurology, Regensburg University, Regensburg, Germany
4 Department of Neurosurgery, Regensburg University Hospital, Regensburg, Germany
5 Isarna Therapeutics GmbH, Munich, Germany
Markus J. Riemenschneider, email:
Keywords: TGF-ß1/2, p-Smad2/3, cancer, glioma, carcinoma, Pathology Section
Received: June 16, 2015 Accepted: August 31, 2015 Published: September 22, 2015
The literature on TGF-ß in cancer including data on the expression or activation of TGF-ß pathway components in specific tumors types is steadily growing. However, no systematic and uniform analysis exists reporting expression levels of the main TGF-ß pathway components across the most frequent tumor types. We used a standardized immunohistochemical assay investigating TGF-ß isoform expression and pathway activation across 13 different tumor types and corresponding non-neoplastic tissues. The study was performed on tissue microarrays allowing for the parallel analysis of a total of 1638 human tumor samples. TGF-ß1, TGF-ß2 and p-Smad2/3 were substantially expressed in multiple cancers widening the options for TGF-ß isoform directed therapies. Of note, TGF-ß antigens appear to be expressed in an individual manner pointing towards a need for patient preselection for TGF-β isoform specific treatment. Yet, a thorough investigation of antibody specificity and assay validity revealed that immunohistochemistry did not correlate with other detection methods on mRNA or protein level in all instances. As such, with the currently available means (i.e. antibodies tested) a stratification of patients within clinical trials for TGF-ß directed antisense therapies based upon TGF-β immunohistochemistry alone has to be interpreted with caution and should be carefully evaluated in combination with other parameters.
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