Abstract
The literature on TGF-beta in cancer including data on the expression or activation of TGF-beta pathway components in specific tumors types is steadily growing. However, no systematic and uniform analysis exists reporting expression levels of the main TGF-beta pathway components across the most frequent tumor types. We used a standardized immunohistochemical assay investigating TGF-beta isoform ...
Abstract
The literature on TGF-beta in cancer including data on the expression or activation of TGF-beta pathway components in specific tumors types is steadily growing. However, no systematic and uniform analysis exists reporting expression levels of the main TGF-beta pathway components across the most frequent tumor types. We used a standardized immunohistochemical assay investigating TGF-beta 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-beta 1, TGF-beta 2 and p-Smad2/3 were substantially expressed in multiple cancers widening the options for TGF-beta isoform directed therapies. Of note, TGF-beta antigens appear to be expressed in an individual manner pointing towards a need for patient preselection for TGF-beta 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-beta directed antisense therapies based upon TGF-beta immunohistochemistry alone has to be interpreted with caution and should be carefully evaluated in combination with other parameters.
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