title: Vascular endothelial growth factor 165b expression in stromal cells and colorectal cancer.
abstract: OBJECTIVE
  To characterize the implications of vascular endothelial growth factor (VEGF)-A in stromal cells and colorectal cancer and the expression of VEGF-A splice variants.
  
  
  METHODS
  VEGF-A expression in tumor and stromal cells from 165 consecutive patients with colorectal cancer was examined by immunohistochemistry. The association between VEGF-A expression status and clinicopathological factors was investigated. Twenty fresh-frozen samples were obtained for laser capture microdissection to analyze the splice variants of VEGF-A.
  
  
  RESULTS
  VEGF-A was expressed in 53.9% and 42.4% of tumor and stromal cells, respectively. VEGF-A expression in tumor cells (t-VEGF-A) was associated with advanced clinical stage (stage 0, 1/9; stage 1, 2/16; stage 2, 32/55; stage 3, 38/66; stage 4, 16/19, P < 0.0001). VEGF-A expression in stromal cells (s-VEGF-A) increased in the earlier clinical stage (stage 0, 7/9; stage 1, 6/16; stage 2, 33/55; stage 3, 22/66; stage 4, 5/19; P = 0.004). Multivariate analyses for risk factors of recurrence showed that only s-VEGF-A expression was an independent risk factor for recurrence (relative risk 0.309, 95% confidence interval 0.141-0.676, P = 0.0033). The five-year disease-free survival (DFS) rates of t-VEGF-A-positive and -negative cases were 51.4% and 62.9%, respectively. There was no significant difference in t-VEGF-A expression status. The five-year DFS rates of s-VEGF-A-positive and -negative cases were 73.8% and 39.9%, respectively. s-VEGF-A-positive cases had significantly better survival than s-VEGF-A-negative cases (P = 0.0005). Splice variant analysis revealed that t-VEGF-A was mainly composed of VEGF165 and that s-VEGF-A included both VEGF165 and VEGF165b. In cases with no venous invasion (v0), the level of VEGF165b mRNA was significantly higher (v0 204.5 ± 122.7, v1 32.5 ± 36.7, v2 2.1 ± 1.7, P = 0.03). The microvessel density tended to be lower in cases with higher VEGF165b mRNA levels.
  
  
  CONCLUSIONS
  s-VEGF-A appears be a good prognostic factor for colorectal cancer and includes VEGF165 and VEGF165b.
authors.affiliation: The First Department of Surgery, Sapporo Medical University, South 1, West 16, Chuo-ku, Sapporo 060-8543, Japan. tayama@sapmed.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Tayama
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Furuhata
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Inafuku
authors.forename: Kenji
authors.initials: K
authors.lastname: Okita
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Nishidate
authors.forename: Toru
authors.initials: T
authors.lastname: Mizuguchi
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Kimura
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D017398:Alternative Splicing; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D061346:Laser Capture Microdissection; D008297:Male; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A