Signal transduction pathway analysis in fibromatosis

Receptor and nonreceptor tyrosine kinases

Justin M.M. Cates, Jennifer O. Black, Doha M. Itani, John H. Fasig, Vicki L. Keedy, Kenneth R. Hande, Brent W. Whited, Kelly Cornett Homlar, Jennifer L. Halpern, Ginger E. Holt, Herbert S. Schwartz, Cheryl M. Coffin

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1711-1718
Number of pages8
JournalHuman Pathology
Volume43
Issue number10
DOIs
StatePublished - Oct 1 2012
Externally publishedYes

Fingerprint

Aggressive Fibromatosis
Fibroma
Receptor Protein-Tyrosine Kinases
Signal Transduction
Cicatrix
Platelet-Derived Growth Factor Receptors
Phosphotransferases
Protein-Tyrosine Kinases
Focal Adhesion Kinase 1
ErbB-2 Receptor
Proto-Oncogene Proteins c-kit
Proto-Oncogene Proteins c-met
Somatomedin Receptors
STAT3 Transcription Factor
Stem Cell Factor
Growth Factor Receptors
Protein-Serine-Threonine Kinases
Insulin Receptor
Mitogen-Activated Protein Kinases
Epidermal Growth Factor Receptor

Keywords

  • Desmoid-type fibromatosis
  • Nonreceptor tyrosine kinase
  • Receptor tyrosine kinase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Cates, J. M. M., Black, J. O., Itani, D. M., Fasig, J. H., Keedy, V. L., Hande, K. R., ... Coffin, C. M. (2012). Signal transduction pathway analysis in fibromatosis: Receptor and nonreceptor tyrosine kinases. Human Pathology, 43(10), 1711-1718. https://doi.org/10.1016/j.humpath.2011.12.021

Signal transduction pathway analysis in fibromatosis : Receptor and nonreceptor tyrosine kinases. / Cates, Justin M.M.; Black, Jennifer O.; Itani, Doha M.; Fasig, John H.; Keedy, Vicki L.; Hande, Kenneth R.; Whited, Brent W.; Homlar, Kelly Cornett; Halpern, Jennifer L.; Holt, Ginger E.; Schwartz, Herbert S.; Coffin, Cheryl M.

In: Human Pathology, Vol. 43, No. 10, 01.10.2012, p. 1711-1718.

Research output: Contribution to journalArticle

Cates, JMM, Black, JO, Itani, DM, Fasig, JH, Keedy, VL, Hande, KR, Whited, BW, Homlar, KC, Halpern, JL, Holt, GE, Schwartz, HS & Coffin, CM 2012, 'Signal transduction pathway analysis in fibromatosis: Receptor and nonreceptor tyrosine kinases', Human Pathology, vol. 43, no. 10, pp. 1711-1718. https://doi.org/10.1016/j.humpath.2011.12.021
Cates, Justin M.M. ; Black, Jennifer O. ; Itani, Doha M. ; Fasig, John H. ; Keedy, Vicki L. ; Hande, Kenneth R. ; Whited, Brent W. ; Homlar, Kelly Cornett ; Halpern, Jennifer L. ; Holt, Ginger E. ; Schwartz, Herbert S. ; Coffin, Cheryl M. / Signal transduction pathway analysis in fibromatosis : Receptor and nonreceptor tyrosine kinases. In: Human Pathology. 2012 ; Vol. 43, No. 10. pp. 1711-1718.
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