Kenneth Hande
Faculty Member
Last active: 3/20/2014

Signal transduction pathway analysis in fibromatosis: receptor and nonreceptor tyrosine kinases.

Cates JM, Black JO, Itani DM, Fasig JH, Keedy VL, Hande KR, Whited BW, Homlar KC, Halpern JL, Holt GE, Schwartz HS, Coffin CM
Hum Pathol. 2012 43 (10): 1711-8

PMID: 22520949 · PMCID: PMC4278590 · DOI:10.1016/j.humpath.2011.12.021

Despite reports of receptor tyrosine kinase activation in desmoid-type fibromatosis, therapeutic benefits of kinase inhibitor therapy are unpredictable. Variability in signal transduction or cellular kinases heretofore unevaluated in desmoid tumors may be responsible for these inconsistent responses. In either case, a better understanding of growth regulatory signaling pathways is necessary to assess the theoretical potential of inhibitor therapy. Immunohistochemical analysis of tyrosine kinases and activated isoforms of downstream signal transduction proteins was performed on a tissue microarray containing 27 cases of desmoid-type fibromatosis and 14 samples of scar; 6 whole sections of normal fibrous tissue were studied for comparison. Platelet-derived growth factor receptor, β type, and focal adhesion kinase 1 were expressed in all desmoid tumors and healing scars but only 80% and 50% of nonproliferative fibrous tissue samples, respectively. Hepatocyte growth factor receptor was detected in 89% of desmoids and all scars tested, but not in any of the fibrous tissue samples. Epidermal growth factor receptor was detected in only 12% of desmoids and not in scar or fibrous tissue. Mast/stem cell growth factor receptor, receptor tyrosine-protein kinase erbB-2, and phosphorylated insulin-like growth factor 1 receptor/insulin receptor were negative in all study cases. Variable levels of phosphorylated downstream signal transduction molecules RAC-α/β/γ serine/threonine-protein kinase, mitogen-activated protein kinase, and signal transducer and activator of transcription-3 were observed in desmoids (58%, 62%, and 67%), scar tissues (100%, 86%, and 86%), and fibrous tissue (33%, 17%, and 17%). These results indicate that tyrosine kinase signaling is active in both fibromatosis and healing scar, but not in most nonproliferating fibrous tissues. Although platelet-derived growth factor receptor, β type, is expressed ubiquitously in desmoids, the kinases driving cell proliferation in desmoids remain unresolved.

Copyright © 2012 Elsevier Inc. All rights reserved.

MeSH Terms (16)

Adolescent Adult Aged Child Child, Preschool Female Fibroma Humans Immunohistochemistry Infant Male Middle Aged Protein-Tyrosine Kinases Signal Transduction Tissue Array Analysis Young Adult

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