Open AccessSignal transduction pathway analysis in desmoid‐type fibromatosis: Transforming growth factor–β, COX 2 and sex steroid receptors
Author(s) -
Mignemi Nicholas A.,
Itani Doha M.,
Fasig John H.,
Keedy Vicki L.,
Hande Kenneth R.,
Whited Brent W.,
Homlar Kelly C.,
Correa Hernan,
Coffin Cheryl M.,
Black Jennifer O.,
Yi Yajun,
Halpern Jennifer L.,
Holt Ginger E.,
Schwartz Herbert S.,
Schoenecker Jonathan G.,
Cates Justin M. M.
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12037
Subject(s) - fibromatosis , transforming growth factor , signal transduction , cancer research , receptor , biology , sex hormone receptor , medicine , immunohistochemistry , endocrinology , growth factor , tamoxifen , growth factor receptor , tissue microarray , estrogen receptor , pathology , cancer , microbiology and biotechnology , breast cancer
Despite reports of sex steroid receptor and COX 2 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 ( TGF β) and bone morphogenetic proteins ( BMP ) are important regulators of fibroblast proliferation and matrix deposition, but little is known about the TGF β 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 TGF β family signaling pathways, β–catenin, sex steroid hormone receptors and COX 2 were assessed using immunohistochemistry; patterns of co–expression were explored via correlational statistical analyses. In addition to β–catenin, immunoreactivity for phosphorylated SMAD 2/3 (indicative of active TGF β signaling) and COX 2 was significantly increased in desmoid tumors compared with healing scar and quiescent fibrous tissue. Low levels of phosphorylated SMAD 1/5/8 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 SMAD 2/3 and COX 2 immunoreactivity might be of diagnostic utility in these tumors. Given the frequency of androgen receptor, estrogen receptor–β and COX 2 co‐expression in desmoid tumors, further assessment of the efficacy of combination pharmacotherapy using hormonal agonists/antagonists together with COX 2 inhibitors should be considered.