Overexpression of c‐H‐ras p21 is correlated with vascular endothelial growth factor expression and neovascularization in advanced gastric carcinoma ¹

Abstract

Background and Aims 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.

Comparative evaluation of microvessel density determined by CD34 or CD105 in benign and malignant gastric lesions

“…Furthermore, the microvessels showing positive staining for CD34 in benign and malignant tissues appeared to be well-formed, highlighting the morphological difference with those stained by CD105. There have been several published studies using various vascular markers, such as CD31, vascular endothelial growth factor, and von Willebrand's factor, to assess MVD and tumor angiogenesis in gastric carcinoma [21][22][23][24]. The consensus is that MVD or the degree of angiogenesis is associated with tumor progression, which is comparable with the current study.…”

Automated oncogene detection in complex protein networks with applications to the MAPK signal transduction pathway

“…Ras and Raf have both been found to be overexpressed in TCR transgenic mice thymic lymphomas, ovarian caners, skin cancers, esophageal cancers and gastric carcinomas [36][37][38][39][40][41][42].…”

Tumor dormancy of primary and secondary cancers

“…Angiogenesis factors such as VEGF promote tumor cell entry into the circulation (102, 103), so angiogenic tumor cells may indirectly promote metastases of neighboring tumor cells. Metastases usually arise from single cells and reflect distinct phenotypes identified in the primary tumor (104–106).…”