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.
OBJECTIVE
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 (chi2 = 15.57, P = 0.001; chi2 = 6.91, P = 0.046), stage I-II (chi2 = 19.22, P = 0.001; chi2 = 16.75, P = 0.001), non-vessel invasion (chi2 = 11.92, P = 0.006; chi2 = 14.15, P = 0.002), non-lymphatic metastasis (chi2 = 28.41, P = 0.001; chi2 = 22.5, P = 0.005) and non-distant metastasis (chi2 = 12.32, P = 0.004; chi2 = 17.42, P = 0.002; chi2 = 11.25, P = 0.012; chi2 = 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 (chi2 = 9.61, P = 0.021), stage I-II (chi2 = 16.66, P = 0.001), non-vessel invasion (chi2 = 29.38, P = 0.001), non-lymphatic metastasis (chi2 = 18.68, P = 0.005), and non-distant metastasis (chi2 = 22.72, P = 0.007; chi2 = 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 > or = 54.9 was significantly shorter than those in cases with negative expression or MVD value < 54.9.


CONCLUSIONS
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.
Zhang
Li
L
Department of Pathology, Wenzhou Medical College, Zhejiang Province, China.
Zhao
Zhong-Sheng
ZS
Ru
Guo-Qing
GQ
Ma
Jie
J
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D018450:Disease Progression; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D013270:Stomach / Q000098:blood supply / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
C524898:PLAUR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D042461:Vascular Endothelial Growth Factor A; D014568:Urokinase-Type Plasminogen Activator