title: Expression of platelet-derived growth factor receptor in low-grade endometrial stromal sarcomas in the absence of activating mutations.
abstract: OBJECTIVE
  To investigate platelet-derived growth factor receptor (PDGFR)alpha and PDGFRbeta expression and a mutational analysis of PDGFRalpha (exons 11, 12, 17 and 18) and PDGFRbeta (exon 12) genes in endometrial stromal sarcomas (ESS). Gastrointestinal stromal tumours (GISTs), which have somatic mutations of the transmembrane tyrosine kinase receptor, respond to tyrosine kinase inhibitors, which act through an inhibitory effect on class 3 receptor tyrosine kinase members such as PDGFRalpha, PDGFRbeta and c-kit.
  
  
  RESULTS
  The immunohistochemical expression of PDGFRalpha and PDGFRbeta was investigated in 37 archival c-kit- ESS. Staining was scored as negative (0-10% positive tumour cells) and positive (weakly positive 11-50% positive cells; strongly positive > 50% positive cells). PDGFRalpha was expressed in 24/37 ESS [65%; strongly by 19/37 (51.5%) and weakly by 5/37 ESS (13.5%)]. ESS tumour cells were negative for PDGFRbeta, but endothelial cells stained positive. A mutational analysis of PDGFRalpha (exons 11, 12, 17 and 18) and PDGFRbeta (exon 12) genes on frozen metastatic ESS from three patients detected no mutations leading to amino acid changes in the mature protein.
  
  
  CONCLUSIONS
  Patients with PDGFRalpha+ ESS may benefit from treatment with tyrosine kinase inhibitors by blocking autocrine and paracrine stimulation loops, blocking neovascularization and enhancing the effects of chemotherapy.
authors: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors: B
authors: B
authors: Liegl
authors: C
authors: C
authors: Gülly
authors: O
authors: O
authors: Reich
authors: F F
authors: FF
authors: Nogales
authors: A
authors: A
authors: Beham
authors: S
authors: S
authors: Regauer
mesh_terms: D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000096:biosynthesis* / Q000235:genetics; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D018203:Sarcoma, Endometrial Stromal / Q000378:metabolism* / Q000473:pathology / Q000556:secondary
chemical_list: D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta