title: Intensity of vascular endothelial growth factor expression is associated with increased risk of recurrence and decreased disease-free survival in papillary thyroid cancer.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells, stimulates angiogenesis, and increases vascular permeability. Increased VEGF expression has been associated with poor clinical outcomes in many malignancies. Several recent reports have documented over expression of VEGF in papillary thyroid cancer. We hypothesized that increased expression of VEGF would be associated with either an increased risk of recurrence or a decreased recurrence-free survival in papillary thyroid cancer.
  
  
  METHODS
  Immunohistochemistry was used to detect VEGF expression in archival paraffin-embedded surgical thyroid specimens from 96 subjects with papillary thyroid cancer.
  
  
  RESULTS
  VEGF expression was detected in 98% (94/96) of the samples, predominantly of slight-to-moderate intensity in the majority of malignant cells. However, the specific finding of a diffuse pattern of intense immunostaining for VEGF was detected significantly more often than less intense, patchy immunostaining patterns in subjects with distant metastasis at diagnosis (63% versus 15%, P =.005), local recurrence (58% versus 13%, P =.001), and distant recurrence (83% versus 14%, P =.001). Furthermore, this specific pattern of diffuse, intense VEGF expression was associated with a significantly shorter recurrence-free survival than other staining patterns (P =.007).
  
  
  CONCLUSIONS
  These data demonstrate that the immunohistochemical pattern of VEGF staining in the initial surgical specimen is strongly associated with the incidence of local and distant metastasis in papillary thyroid cancer.
authors.affiliation: Departments of Otolaryngology, Clinical Investigation and Pediatrics,Walter Reed Army Medical Center, Washington, DC, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Lennard
authors.forename: A
authors.initials: A
authors.lastname: Patel
authors.forename: J
authors.initials: J
authors.lastname: Wilson
authors.forename: B
authors.initials: B
authors.lastname: Reinhardt
authors.forename: C
authors.initials: C
authors.lastname: Tuman
authors.forename: C
authors.initials: C
authors.lastname: Fenton
authors.forename: E
authors.initials: E
authors.lastname: Blair
authors.forename: G L
authors.initials: GL
authors.lastname: Francis
authors.forename: R M
authors.initials: RM
authors.lastname: Tuttle
mesh_terms: D000328:Adult; D002291:Carcinoma, Papillary / Q000737:chemistry / Q000401:mortality* / Q000473:pathology*; D015331:Cohort Studies; D018572:Disease-Free Survival; D016228:Endothelial Growth Factors / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000401:mortality* / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors