title: Expression of vascular endothelial growth factor (VEGF)-D and its receptor, VEGF receptor 3, as a prognostic factor in endometrial carcinoma.
abstract: OBJECTIVE
  To evaluate the prognostic value of vascular endothelial growth factor (VEGF)-D and VEGF receptor (VEGFR)-3 in endometrial carcinoma.
  
  
  METHODS
  We assessed the levels of immunoreactivity for VEGF-D and VEGFR-3 in 71 endometrial carcinomas, 14 complex atypical endometrial hyperplasias, and 16 normal endometria by immunohistochemistry.
  
  
  RESULTS
  VEGF-D was stained in both tumor cells and adjacent stromal cells. VEGFR-3 was stained in both tumor cells and adjacent endothelial cells. Immunoreactivity for VEGF-D in tumor cells and adjacent stromal cells became significantly stronger as lesions progressed from normal endometrium to advanced carcinoma. Similarly, immunoreactivity for VEGFR-3 in tumor cells and adjacent endothelial cells was significantly greater as lesions progressed from normal endometrium to advanced carcinoma. A strong correlation was found between high levels of VEGF-D immunoreactivity in carcinoma cells and VEGFR-3 in both carcinoma cells and adjacent endothelial cells. Similarly, high levels of VEGF-D immunoreactivity in stromal cells were significantly correlated with those of VEGFR-3 in both carcinoma cells and endothelial cells. High levels of VEGF-D in carcinoma cells and stromal cells, as well as those of VEGFR-3 in carcinoma cells and endothelial cells, were significantly related to myometrial invasion and lymph node metastasis. A strong correlation was found between poor survival and high levels of VEGF-D in both carcinoma cells and stromal cells and between poor survival and high levels of VEGFR-3 in carcinoma cells. Moreover, the high levels of VEGF-D in stromal cells and VEGFR-3 in carcinoma cells were independent prognostic factors in endometrial carcinoma.
  
  
  CONCLUSIONS
  The presence of VEGF-D and VEGFR-3 in endometrial carcinoma may predict myometrial invasion and lymph node metastasis and may prospectively identify patients who are at increased risk for poor outcome. In addition, VEGF-D and VEGFR-3 may be promising targets for new therapeutic strategies in endometrial carcinoma.
authors.affiliation: Reproductive Molecular Research Group, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom. yokoyama@cc.hirosaki-u.ac.jp
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: D Stephen
authors.initials: DS
authors.lastname: Charnock-Jones
authors.forename: Diana
authors.initials: D
authors.lastname: Licence
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yanaihara
authors.forename: Julie M
authors.initials: JM
authors.lastname: Hastings
authors.forename: Cathrine M
authors.initials: CM
authors.lastname: Holland
authors.forename: Makoto
authors.initials: M
authors.lastname: Emoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Tomomi
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Maruyama
authors.forename: Shigemi
authors.initials: S
authors.lastname: Sato
authors.forename: Hideki
authors.initials: H
authors.lastname: Mizunuma
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Smith
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000175:diagnosis / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis; D012306:Risk; D016896:Treatment Outcome; D042643:Vascular Endothelial Growth Factor D / Q000096:biosynthesis*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000096:biosynthesis*
chemical_list: D042643:Vascular Endothelial Growth Factor D; D040321:Vascular Endothelial Growth Factor Receptor-3