The association of kappa-ras gene mutation and vascular endothelial growthfactor gene expression in pancreatic carcinoma

Background. Previously, the authors reported the role of the vascular endot helial growth factor (VEGF) as an angiogenic factor in 40 patients with pan creatic carcinoma. In this study, they investigated the mechanism underlyin g the regulation of VEGF gene expression and evaluated EGF expression and K -ras gene status in 48 patients with pancreatic carcinoma. Methods. The authors used quantitative reverse transcriptase-polymerase cha in reaction analysis and direct sequencing techniques for a retrospective s tudy of VEGF gene expression and K-ras gene status in tumor tissue samples from 48 patients with pancreatic carcinoma. Immunohistochemistry also was u sed to investigate VEGF protein expression. Results. Thirty-one tumors (64.6%) were evaluated with high VEGF expression , and 17 tumors (35.4%) were evaluated with low VEGF expression. Of the 48 primary pancreatic tumors studied, 33 tumors (68.8%) contained mutations of the K-ras gene. There was a significant correlation between T-GF expressio n and K-ras status. Twenty-five of 33 tumors (75.8%) with mutant K-ras gene s showed high VEGF expression, whereas only 6 of 15 tumors with the wild ty pe K-ras (40.0%) showed high VEGF expression (P = 0.038). The mean (+/- sta ndard error) VEGF conservation rate for the 33 tumors with mutant K-ras was 1.839 +/- 1.241, and that for the 15 tumors with wild type K-ras was 1.057 +/- 0.983 (P = 0.037). Furthermore, the median survival for patients with mutant K-ras was shorter than for those with wild type K-ras (10.6 months v s. 27.6 months, respectively; P = 0.026), whereas the median survival for p atients with high VEGF expression was shorter compared with that for patien ts with low VEGF expression (9.5 months vs. 26.4 months, respectively; P = 0.002). Cox regression model analysis indicated that only the VEGF status w as a significant factor for prognosis (P = 0.024). Other variables, i.e., K -ras status, histopathologic tumor grade, tumor status, lymph node status, metastatic status, gender, and age at surgery, were not significant. Conclusions. The results of this study suggest that K-ras oncogene mutation may be associated with VEGF expression and that patients with pancreatic c arcinoma who have high VEGF expression are associated with a poor prognosis . Cancer2001; 92:488-99. (C) 2001 American Cancer Society.