Overexpression of c-H-ras p21 is correlated with vascular endothelial growth factor expression and neovascularization in advanced gastric carcinoma.
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.
Kim
Y B
YB
Department of Pathology, Inha University College of Medicine, Inchon, Korea. ybkim@madang.ajou.ac.kr
Han
J Y
JY
Kim
T S
TS
Kim
P S
PS
Chu
Y C
YC
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
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)