Overexpression of EphA2, MMP‐9, and MVD‐CD34 in hepatocellular carcinoma: Implications for tumor progression and prognosis

AIM: 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.