Gastric Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jul 7, 2006; 12(25): 3970-3976
Published online Jul 7, 2006. doi: 10.3748/wjg.v12.i25.3970
Correlative studies on uPA mRNA and uPAR mRNA expression with vascular endothelial growth factor, microvessel density, progression and survival time of patients with gastric cancer
Li Zhang, Zhong-Sheng Zhao, Guo-Qing Ru, Jie Ma
Li Zhang, Department of Pathology, Wenzhou Medical College, Wenzhou 325000, Zhejiang Province, China
Zhong-Sheng Zhao, Jie Ma, Guo-qing Ru, Department of Pathology, Zhejiang Provincial Hospital, Hangzhou 310014, Zhejiang Province, China
Li Zhang, Shaoxing University Medical College, Shaoxing 312000, Zhejiang Province, China
Author contributions: All authors contributed equally to the work.
Supported by the grant from Zhejiang Province Natural Science Foundation, No. M303843
Correspondence to: Dr. Zhong-Sheng Zhao, Department of Pathology, Zhejiang Provincial Hospital, Hangzhou 310014, Zhejiang Province, China. fyzl7618@hotmail.com
Telephone: +86-571-85893289
Received: February 15, 2006
Revised: March 20, 2006
Accepted: March 27, 2006
Published online: July 7, 2006
Abstract

AIM: To investigate the correlations between the expression of urokinase-type plasminogen activator (uPA) mRNA, uPA receptor (uPAR) mRNA and vascular endothelial growth factor (VEGF) protein and clinicopathologic features, microvessel density (MVD) and survival time.

METHODS: In situ hybridization and immuno-histochemistry techniques were used to study the expressions of uPA mRNA, uPAR mRNA, VEGF and CD34 protein in 105 gastric carcinoma specimens.

RESULTS: Expressions of uPA mRNA, uPAR mRNA and VEGF protein were observed in 61 (58.1%) cases, 70 (66.7%) cases and 67 (63.8%) cases, respectively. The uPA mRNA and uPAR mRNA positive expression rates in infiltrating-type cases (73.7%, 75.4%), stage III-IV (72.1%, 75.4%), vessel invasion (63.2%, 69.9%), lymphatic metastasis (67.1%, 74.4%) and distant metastasis (88.1%, 85.7%) were significantly higher than those of the expanding-type (χ2 = 15.57, P = 0.001; χ2 = 6.91, P = 0.046), stage I-II (χ2 = 19.22, P = 0.001; χ2 = 16.75, P = 0.001), non-vessel invasion (χ2 = 11.92, P = 0.006; χ2 = 14.15, P = 0.002), non-lymphatic metastasis (χ2 = 28.41, P = 0.001; χ2 = 22.5, P = 0.005) and non-distant metastasis (χ2 = 12.32, P = 0.004; χ2 = 17.42, P = 0.002; χ2 = 11.25, P = 0.012; χ2 = 18.12, P = 0.002).The VEGF positive expression rates in infiltrating-type cases (75.4%), stage III-IV (88.5%), vessel invasion (82.9%), lymphatic metastasis (84.3%) and distant metastasis (95.2%) were significantly higher than those of the expanding-type (χ2 = 9.61, P = 0.021), stage I-II (χ2 = 16.66, P = 0.001), non-vessel invasion (χ2 = 29.38, P = 0.001), non-lymphatic metastasis (χ2 = 18.68, P = 0.005), and non-distant metastasis (χ2 = 22.72, P = 0.007; χ2 = 21.62, P = 0.004). The mean MVD in the specimens positive for the uPA mRNA, uPAR mRNA and VEGF protein was markedly higher than those with negative expression groups. Moreover, a positive relation between MVD and uPA mRNA (rs = 0.199, P = 0.042), uPAR mRNA (rs = 0.278, P = 0.035), and VEGF (rs = 0.398, P = 0.048) expressions was observed. The mean survival time in cases with positive uPA mRNA, uPAR mRNA and VEGF protein expression or MVD value ≥ 54.9 was significantly shorter than those in cases with negative expression or MVD value < 54.9.

CONCLUSION: uPA and uPAR expressions are correlated with enhanced VEGF-induced tumor angiogenesis and may play a role in invasion and nodal metastasis of gastric carcinoma, thereby serving as prognostic markers of gastric cancer.

Keywords: Stomach neoplasm; Urokinase-type plasminogen activator; Urokinase-type plasminogen activator receptor; Vascular endothelial growth factor; Prognosis