title: Endometrial stromal tumors: immunohistochemical and molecular analysis of potential targets of tyrosine kinase inhibitors.
abstract: BACKGROUND
  The systemic treatment of malignant endometrial stromal tumors (EST) is not well established. A few reports describe objective responses to imatinib, which suggest a novel therapeutic strategy for these tumors. Due to these facts, we aimed to perform a retrospective analysis of possible molecular targets of tyrosine kinase inhibitors (TKI) in EST: KIT, PDGFRA and EGFR.
  
  
  METHODS
  52 endometrial stromal sarcomas and 13 undifferentiated endometrial sarcomas were examined and reviewed. Mutational analysis were performed for exons 9, 11, 13, and 17 of the KIT gene, exons 12 and 18 of the PDGFRA gene and exons 18, 19, 20 and 21 of the EGFR gene. The incidence and distribution of the KIT, PDGFRA, and EGFR expression were examined by immunohistochemistry, and EGFR amplification was assessed by fluorescence in situ hybridization.
  
  
  RESULTS
  No mutations in KIT, PDGFRA and EGFR genes were detected. Overexpression of KIT, PDGFRA, EGFR, was detected in 2 (3%), 23 (35.4%), 7 (10.8%) cases respectively, whereas amplification of EGFR gene was not found.
  
  
  CONCLUSIONS
  Absence of significant expression, amplification and activating mutations on these tyrosine kinase receptors suggest that it is unlikely that EST can benefit from therapies such as TKI on the systemic setting.
authors.affiliation: Pathology Department, Hospital Espírito Santo E.P.E, Évora, Portugal.
authors.forename: Ruth
authors.initials: R
authors.lastname: Sardinha
authors.affiliation: Centro de Investigación del Cáncer-IBMCC USAL-CSIC, Salamanca, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Hernández
authors.affiliation: Centro de Investigación del Cáncer-IBMCC USAL-CSIC, Salamanca, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Fraile
authors.affiliation: Pathology Department, USP-Institut Universitari Dexeus, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Tresserra
authors.affiliation: Pathology Department, Hospital de Bellvitge, Barcelona, Spain.
authors.forename: August
authors.initials: A
authors.lastname: Vidal
authors.affiliation: Pathology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors.forename: Maria Carmén
authors.initials: MC
authors.lastname: Gómez
authors.affiliation: Pathology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Aurora
authors.initials: A
authors.lastname: Astudillo
authors.affiliation: Anatomical Pathology Department, Hospital Universitario de la Laguna, Canarias, Spain.
authors.forename: Nieves
authors.initials: N
authors.lastname: Hernández
authors.affiliation: Pathology Department, Complejo Hospitalario Universitario de Badajoz, Badajoz, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Saenz de Santamaría
authors.affiliation: Pathology Department, Hospital Clinic de Barcelona, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Ordi
authors.affiliation: Pathology Department, Hospital do Espírito Santo E.P.E, Évora, Portugal.
authors.forename: Luis
authors.initials: L
authors.lastname: Gonçalves
authors.affiliation: Pathology Department, Hospital Son Espases, Palma de Mallorca, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Ramos
authors.affiliation: Medical Oncology Service, Catalan Institute of Oncology - Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Balañá
authors.affiliation: Centro de Investigación del Cáncer-IBMCC USAL-CSIC, Salamanca, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: de Álava