Overexpression of EphA2, MMP-9, and MVD-CD34 in hepatocellular carcinoma: Implications for tumor progression and prognosis.
OBJECTIVE
To investigate the expression of erythropoietin-producing hepatocellular (Eph)A2 receptor, matrix metalloproteinase (MMP)-9, and angiogenesis in hepatocellular carcinoma (HCC), in order to reveal their expression correlations with tumor invasion, metastasis, and prognosis.


METHODS
From January 2000 to June 2003, 129 specimens of resected tumors from the patients with HCC were obtained. Corresponding pericarcinomatous liver tissues were also obtained and selected as a control group. Expressions of EphA2, MMP-9, and CD34 were detected with immunohistochemical staining. Microvascular density (MVD) was calculated with counting of CD34-positive vascular endothelial cells.


RESULTS
The expressions of EphA2, MMP-9, and MVD in the HCC tissues were significantly higher than those in the pericarcinomatous liver tissues (P < 0.01). Statistical analysis showed there were significant correlations between the expressions of EphA2, MMP-9 and MVD in some classicclinicopathological parameters (i.e. tumor nodule, vein invasion, tumor, node, metastasis stages, extrahepatic metastasis; P < 0.05). The correlation between EphA2 and MMP-9 expression was positive (r = 0.625, P = 0.011). Tumor MVD was closely associated with EphA2 (r = 0.281, P = 0.01) and MMP-9 (r = 0.319, P < 0.01) expressions. In particular, EphA2, MMP-9, and MVD expressions levels were found to be independent prognostic factors after HCC resection.


CONCLUSIONS
Overexpressions of EphA2 and MMP-9 relate to tumor progression, metastasis, and prognosis in HCC. The present study suggests that EphA2 is associated with key mediators of angiogenesis and invasion.
Yang
Pu
P
Hepatobiliary & Enteric Surgery Research Center, Xiangya Hospital, Central South University, Xiangya Road, Changsha 410008, Hunan Province, China.
Yuan
Weijie
W
He
Jiantai
J
Wang
Jiwei
J
Yu
Li
L
Jin
Xin
X
Hu
Yu
Y
Liao
Mingmei
M
Chen
Zihua
Z
Zhang
Yangde
Y