Expression Of VEGF, COX-2 And PTEN Protein And Its Correlation With Prognosis In Hepatocellular Carcinoma

Objective: To investigate the expression of VEGF. COX-2 andPTEN proteins and their relationships in patients ofhepatocellular carcinoma (HCC) and analyse the clinicalsignificance with patient's prognosis.Methods: 68 patients with HCC who underwent surgicalresction between 1988 and 1997 at the Fist Affiliated Hospitalof JiNan university were followed up. VEGF,COX-2 and PTENproteins were examined by immunohistochemical technique withSP or SAP-method, and the tissue microvascular density (MVD)was measused in all 68 cases of HCC tissue specimens. Therelationship of VEGF,COX-2 and PTEN and their relationshipwith clinical and biologic factoesand prognosis was analyzedby SPSS 12.0. 32 paracancerous tissues and 10 cases hepatictissues were selected as normal controls.Results: The positive rates of VEGF, COX-2 and PTEN proteinsin HCC tissues were 63.2% (43/68), 75% (51/68) and 45.6% (31/68)respectively. Expression of VEGF was positively correlatedwith expression of COX-2 (P＜0.05), the positive expressionsof VEGF and COX-2 were positively correlated with negativeexpression of PTEN (P＜0.05). The frequencies of VEGF,COX-2and PTEN protein positively in corresponding paracancerous tissues, respectively were 15.6％(5/32), 9.4％(3/32) and 100％(32/32).There was negative expression of VEGF,COX-2 in 10cases hepatic tissues, but positive expression of PTEN.Therewas a significant difference in VEGF,COX-2 and PTEN proteinexpression between HCC and paracancerous tissues (P＜0.05).Expression of PTEN was detected in normal hepatic tissue, butVEGF and COX-2 could not be detected in normal hepatictissues. But it was not detected in HCC or only. Eexpression ofVEGF was posiyively correlated with that of COX-2; Expressionof PTEN was negatively correlated withthat of VEGF and COX-2.Higher expression of VEGF and COX-2, and higher MVD but lowerexpression of PTEN showed a significantly positive correlationwith vascular invasion and metastasis. Kaplan-Meier survivalcurves showed the survival time of patients with positively ofVEGFand COX-2 were shorter than those with negativelyexpression of VEGF and COX-2, Log-rank test, P＜0.05. but thesurvival time of patients with highly expression of PTEN weresiginifcantly longer than those with reduced expression of PTEN,Log-rank test, P＜0.05. According to Cox's hazards analysis,univariate analysis found that prognosis of patients with HCCwas significantly correlated with patients'year elder, HCCsizes, MVD, vascular invasion, distant metastasis, and expression of VEGF,COX-2, PTEN. Multivariate analysis foundthat HCC sizes, vascular invasion, and higher expression ofCOX-2,negative expression of mutant PTEN protein wereindependent risk factors and related to the reducing ofsurvival.Conclusion: There is a higher expression rate of VEGF,COX-2proteins and lower expression rate of PTEN in HCC byimmunohistochemical technique detecting. Expression of PTENsignificantly correlated with that of VEGF and COX-2.Expression of VEGF,COX-2 and PTEN significantly withbiological features of HOe. For example:the positiveexpression of VEGF,COX-2 and negative expression of PTENprotein are related to vascular invasion and metastasis in HCC.They may be used as the useful predictor of poor prognosis inpatients with HCC.