title: Overexpression of c-H-ras p21 is correlated with vascular endothelial growth factor expression and neovascularization in advanced gastric carcinoma.
abstract: OBJECTIVE
  ras Gene and its product (p21) have been reported to be associated with vascular endothelial growth factor (VEGF), which is one of the most important angiogenic factors, and tumor-associated angiogenesis. We tried to evaluate the correlation between the expression of c-H-ras gene product p21 and angiogenesis in advanced gastric carcinoma.
  
  
  METHODS
  Immunohistochemical expression of c-H-ras p21 and VEGF was examined in 49 advanced gastric adenocarcinomas. In addition, double immunohistochemical staining was performed using anti-CD34 and anti-Ki-67 antibodies, and the intratumoral microvessel densities and their endothelial proliferative labeling indices were then counted to evaluate the degree of angiogenesis.
  
  
  RESULTS
  The expression of c-H-ras p21 was demonstrated in 43 out of 49 gastric adenocarcinomas (87.8%). It did not correlate with histologic type, depth of invasion or metastasis. However, the degree of c-H-ras p21 expression was correlated with VEGF. In addition, the degree of c-H-ras p21 expression was correlated with increased intratumoral microvascular density and endothelial proliferative activity.
  
  
  CONCLUSIONS
  We suggest that c-H-ras oncogene product p21 contributes to the upregulation of tumor-associated angiogenesis by the increased production of VEGF in advanced gastric carcinomas. Therefore, treatment involving the targeting of ras oncogene could inhibit solid tumor growth by suppressing tumor-associated angiogenesis.
authors.affiliation: Department of Pathology, Inha University College of Medicine, Inchon, Korea. ybkim@madang.ajou.ac.kr
authors.forename: Y B
authors.initials: YB
authors.lastname: Kim
authors.forename: J Y
authors.initials: JY
authors.lastname: Han
authors.forename: T S
authors.initials: TS
authors.lastname: Kim
authors.forename: P S
authors.initials: PS
authors.lastname: Kim
authors.forename: Y C
authors.initials: YC
authors.lastname: Chu
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply* / Q000378:metabolism*; D000328:Adult; D000368:Aged; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / 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; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)