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• W2077369044 endingPage "2180" @default.
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• W2077369044 abstract "Despite reports of sex steroid receptor and COX2 expression in desmoid-type fibromatosis, responses to single agent therapy with anti-estrogens and non-steroidal anti-inflammatory drugs are unpredictable. Perhaps combination pharmacotherapy might be more effective in desmoid tumors that co-express these targets. Clearly, further understanding of the signaling pathways deregulated in desmoid tumors is essential for the development of targeted molecular therapy. Transforming growth factor-β (TGFβ) and bone morphogenetic proteins (BMP) are important regulators of fibroblast proliferation and matrix deposition, but little is known about the TGFβ superfamily in fibromatosis. A tissue microarray representing 27 desmoid tumors was constructed; 14 samples of healing scar and six samples of normal fibrous tissue were included for comparison. Expression of selected receptors and activated downstream transcription factors of TGFβ family signaling pathways, β-catenin, sex steroid hormone receptors and COX2 were assessed using immunohistochemistry; patterns of co-expression were explored via correlational statistical analyses. In addition to β-catenin, immunoreactivity for phosphorylated SMAD2/3 (indicative of active TGFβ signaling) and COX2 was significantly increased in desmoid tumors compared with healing scar and quiescent fibrous tissue. Low levels of phosphorylated SMAD1/5/8 were detected in only a minority of cases. Transforming growth factor-β receptor type 1 and androgen receptor were expressed in both desmoid tumors and scar, but not in fibrous tissue. Estrogen receptor-β was present in all cases studied. Transforming growth factor-β signaling appears to be activated in desmoid-type fibromatosis and phosphorylated SMAD2/3 and COX2 immunoreactivity might be of diagnostic utility in these tumors. Given the frequency of androgen receptor, estrogen receptor-β and COX2 co-expression in desmoid tumors, further assessment of the efficacy of combination pharmacotherapy using hormonal agonists/antagonists together with COX2 inhibitors should be considered." @default.
• W2077369044 created "2016-06-24" @default.
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• W2077369044 date "2012-11-15" @default.
• W2077369044 modified "2023-10-12" @default.
• W2077369044 title "Signal transduction pathway analysis in desmoid-type fibromatosis: Transforming growth factor-β, COX2 and sex steroid receptors" @default.
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• W2077369044 doi "https://doi.org/10.1111/cas.12037" @default.
• W2077369044 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4278584" @default.
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• W2077369044 hasPublicationYear "2012" @default.
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