Expression and mutational analysis of tyrosine kinase receptors c-kit, PDGFRα, and PDGFRβ in ovarian cancers

Sharon P. Wilczynski, Yuan Yuan Chen, Wengang Chen, Stephen B. Howell, John E. Shively, David S Alberts

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Most women with epithelial ovarian cancer are diagnosed with advanced disease. Despite surgery and initial tumor reduction by standard chemotherapy, the tumors frequently recur and the patients eventually die of their disease. New drugs that inhibit tyrosine kinase receptors (TKRs) are being investigated for treatment and this study was undertaken to determine the expression and mutational state for 3 TKRs (c-kit, platelet-derived growth factor receptor [PDGFR] α, and PDGFRβ) in ovarian cancer. Tissue arrays containing 84 epithelial ovarian tumors were studied by immunohistochemistry with antibodies specific for c-kit, PDGFRα, and PDGFRβ. Immunoreactivity was detected in 78% of the tumor to at least one TKR. PDGFRα was expressed in the largest percentage of ovarian tumors (58%) whereas 29% expressed PDGFRβ. Two commercial antibodies against c-kit were studied and 33% of the tumors stained with one but only 6% were interpreted as positive with the second antibody. Activation of TKRs may occur through mutations but, by sequence analysis, no mutations were detected in 6 ovarian tumors with elevated immunoreactivity for each of the TKRs (c-kit, PDGFRα, and PDGFRβ). Tyrosine kinase receptors could also be activated through autocrine or paracrine stimulation of receptor by its ligand. Of 43 (35%) tumors tested for both c-kit receptor and its ligand (stem cell factor), 15 expressed both proteins indicating the possibility that this autocrine stimulation feedback loop is a factor in the growth of some ovarian cancers. This study demonstrates that PDGFRα, PDGFRβ, and c-kit are expressed in a high percentage of epithelial ovarian cancers suggesting that tyrosine kinase inhibitors may be useful in the treatment of these tumors.

Original languageEnglish (US)
Pages (from-to)242-249
Number of pages8
JournalHuman Pathology
Volume36
Issue number3
DOIs
StatePublished - Mar 2005

Fingerprint

Platelet-Derived Growth Factor Receptors
Receptor Protein-Tyrosine Kinases
Ovarian Neoplasms
Neoplasms
Antibodies
Proto-Oncogene Proteins c-kit
Ligands
Mutation
Stem Cell Factor
Protein-Tyrosine Kinases
Sequence Analysis
Intercellular Signaling Peptides and Proteins
Immunohistochemistry

Keywords

  • c-kit
  • Ovarian cancer
  • Platelet-derived growth factor receptor
  • Tyrosine kinase receptors

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Expression and mutational analysis of tyrosine kinase receptors c-kit, PDGFRα, and PDGFRβ in ovarian cancers. / Wilczynski, Sharon P.; Chen, Yuan Yuan; Chen, Wengang; Howell, Stephen B.; Shively, John E.; Alberts, David S.

In: Human Pathology, Vol. 36, No. 3, 03.2005, p. 242-249.

Research output: Contribution to journalArticle

Wilczynski, Sharon P. ; Chen, Yuan Yuan ; Chen, Wengang ; Howell, Stephen B. ; Shively, John E. ; Alberts, David S. / Expression and mutational analysis of tyrosine kinase receptors c-kit, PDGFRα, and PDGFRβ in ovarian cancers. In: Human Pathology. 2005 ; Vol. 36, No. 3. pp. 242-249.
@article{7757810b72b040e5b6592056b8f87090,
title = "Expression and mutational analysis of tyrosine kinase receptors c-kit, PDGFRα, and PDGFRβ in ovarian cancers",
abstract = "Most women with epithelial ovarian cancer are diagnosed with advanced disease. Despite surgery and initial tumor reduction by standard chemotherapy, the tumors frequently recur and the patients eventually die of their disease. New drugs that inhibit tyrosine kinase receptors (TKRs) are being investigated for treatment and this study was undertaken to determine the expression and mutational state for 3 TKRs (c-kit, platelet-derived growth factor receptor [PDGFR] α, and PDGFRβ) in ovarian cancer. Tissue arrays containing 84 epithelial ovarian tumors were studied by immunohistochemistry with antibodies specific for c-kit, PDGFRα, and PDGFRβ. Immunoreactivity was detected in 78{\%} of the tumor to at least one TKR. PDGFRα was expressed in the largest percentage of ovarian tumors (58{\%}) whereas 29{\%} expressed PDGFRβ. Two commercial antibodies against c-kit were studied and 33{\%} of the tumors stained with one but only 6{\%} were interpreted as positive with the second antibody. Activation of TKRs may occur through mutations but, by sequence analysis, no mutations were detected in 6 ovarian tumors with elevated immunoreactivity for each of the TKRs (c-kit, PDGFRα, and PDGFRβ). Tyrosine kinase receptors could also be activated through autocrine or paracrine stimulation of receptor by its ligand. Of 43 (35{\%}) tumors tested for both c-kit receptor and its ligand (stem cell factor), 15 expressed both proteins indicating the possibility that this autocrine stimulation feedback loop is a factor in the growth of some ovarian cancers. This study demonstrates that PDGFRα, PDGFRβ, and c-kit are expressed in a high percentage of epithelial ovarian cancers suggesting that tyrosine kinase inhibitors may be useful in the treatment of these tumors.",
keywords = "c-kit, Ovarian cancer, Platelet-derived growth factor receptor, Tyrosine kinase receptors",
author = "Wilczynski, {Sharon P.} and Chen, {Yuan Yuan} and Wengang Chen and Howell, {Stephen B.} and Shively, {John E.} and Alberts, {David S}",
year = "2005",
month = "3",
doi = "10.1016/j.humpath.2004.11.009",
language = "English (US)",
volume = "36",
pages = "242--249",
journal = "Human Pathology",
issn = "0046-8177",
publisher = "W.B. Saunders Ltd",
number = "3",

}

TY - JOUR

T1 - Expression and mutational analysis of tyrosine kinase receptors c-kit, PDGFRα, and PDGFRβ in ovarian cancers

AU - Wilczynski, Sharon P.

AU - Chen, Yuan Yuan

AU - Chen, Wengang

AU - Howell, Stephen B.

AU - Shively, John E.

AU - Alberts, David S

PY - 2005/3

Y1 - 2005/3

N2 - Most women with epithelial ovarian cancer are diagnosed with advanced disease. Despite surgery and initial tumor reduction by standard chemotherapy, the tumors frequently recur and the patients eventually die of their disease. New drugs that inhibit tyrosine kinase receptors (TKRs) are being investigated for treatment and this study was undertaken to determine the expression and mutational state for 3 TKRs (c-kit, platelet-derived growth factor receptor [PDGFR] α, and PDGFRβ) in ovarian cancer. Tissue arrays containing 84 epithelial ovarian tumors were studied by immunohistochemistry with antibodies specific for c-kit, PDGFRα, and PDGFRβ. Immunoreactivity was detected in 78% of the tumor to at least one TKR. PDGFRα was expressed in the largest percentage of ovarian tumors (58%) whereas 29% expressed PDGFRβ. Two commercial antibodies against c-kit were studied and 33% of the tumors stained with one but only 6% were interpreted as positive with the second antibody. Activation of TKRs may occur through mutations but, by sequence analysis, no mutations were detected in 6 ovarian tumors with elevated immunoreactivity for each of the TKRs (c-kit, PDGFRα, and PDGFRβ). Tyrosine kinase receptors could also be activated through autocrine or paracrine stimulation of receptor by its ligand. Of 43 (35%) tumors tested for both c-kit receptor and its ligand (stem cell factor), 15 expressed both proteins indicating the possibility that this autocrine stimulation feedback loop is a factor in the growth of some ovarian cancers. This study demonstrates that PDGFRα, PDGFRβ, and c-kit are expressed in a high percentage of epithelial ovarian cancers suggesting that tyrosine kinase inhibitors may be useful in the treatment of these tumors.

AB - Most women with epithelial ovarian cancer are diagnosed with advanced disease. Despite surgery and initial tumor reduction by standard chemotherapy, the tumors frequently recur and the patients eventually die of their disease. New drugs that inhibit tyrosine kinase receptors (TKRs) are being investigated for treatment and this study was undertaken to determine the expression and mutational state for 3 TKRs (c-kit, platelet-derived growth factor receptor [PDGFR] α, and PDGFRβ) in ovarian cancer. Tissue arrays containing 84 epithelial ovarian tumors were studied by immunohistochemistry with antibodies specific for c-kit, PDGFRα, and PDGFRβ. Immunoreactivity was detected in 78% of the tumor to at least one TKR. PDGFRα was expressed in the largest percentage of ovarian tumors (58%) whereas 29% expressed PDGFRβ. Two commercial antibodies against c-kit were studied and 33% of the tumors stained with one but only 6% were interpreted as positive with the second antibody. Activation of TKRs may occur through mutations but, by sequence analysis, no mutations were detected in 6 ovarian tumors with elevated immunoreactivity for each of the TKRs (c-kit, PDGFRα, and PDGFRβ). Tyrosine kinase receptors could also be activated through autocrine or paracrine stimulation of receptor by its ligand. Of 43 (35%) tumors tested for both c-kit receptor and its ligand (stem cell factor), 15 expressed both proteins indicating the possibility that this autocrine stimulation feedback loop is a factor in the growth of some ovarian cancers. This study demonstrates that PDGFRα, PDGFRβ, and c-kit are expressed in a high percentage of epithelial ovarian cancers suggesting that tyrosine kinase inhibitors may be useful in the treatment of these tumors.

KW - c-kit

KW - Ovarian cancer

KW - Platelet-derived growth factor receptor

KW - Tyrosine kinase receptors

UR - http://www.scopus.com/inward/record.url?scp=15544384846&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15544384846&partnerID=8YFLogxK

U2 - 10.1016/j.humpath.2004.11.009

DO - 10.1016/j.humpath.2004.11.009

M3 - Article

C2 - 15791568

AN - SCOPUS:15544384846

VL - 36

SP - 242

EP - 249

JO - Human Pathology

JF - Human Pathology

SN - 0046-8177

IS - 3

ER -