The Study On The Prediction Equation Of Early Recurrence And Metastasis Of Small Hepatocelluar Carcinoma After Curative Hepatic Resection

ObjectiveTo investigate respectively the correlationship of the p53, nm23, p27, uPA,HIF-1α, MMP-9, VEGF, β-catenin, E-cadherin, CK19, Survivin, TGFβ1, PCNAexpression and clinical pathological features between the early recurrence andmetastasis of small hepatocellular carcinoma after radical resection and no recurrencegroup, and estabilsh the corresponding prediction equation.MethodsTo collect liver cancer tissues and adjacent tissues of80cases of smallhepatocellular carcinoma (diameter≤5cm) after radical surgical resection fromJanuary2008to January2011at First Affiliated Hospital of Fujian Medical University(postoperative early recurrence and metastasis of32cases, norecurrence in48cases),and normal liver tissue specimens of14cases. Hand-made tissue chips wereconstructed, which contained hepatoma tissues, non-neoplastic adjacent liver tissuesand normal liver tissues. Immunohistochemical method(IHC) was used to detect theexpression of the p53, nm23, p27, uPA, HIF-1α, MMP-9, VEGF, β-catenin,E-cadherin, CK19, Survivin, TGFβ1, PCNA in the tissue chips. The relationshipbetween their expression, clinicalpathological features and early postoperativerecurrence and metastasis of small hepatocellular carcinoma were analyzed byunivariate and multivariate logistic regression analysis and to establish the predictionequation of early recurrence and metastasis.Results1. Tissue microarrays constructed manually had a very good quality. By IHC, themean fall rate was5.42%and the mean observation rate was100.00%.2. The expression of PCNA, Survivin, CK19, uPA of p53, HIF-1α and the abnormal expression of beta-catenin, E-cadherin in HCC tissues were significantlyhigher than that in normal liver tissue and adjacent tissues (P＜0.05), p27,nm23expression was significantly lower than that in normal liver tissues and adjacent livertissue(P＜0.05), TGFβ1, MMP-9and VEGF expression were significantly higherthan that in the normal liver tissue (P＜0.05).3. By univariate analysis, tumor size, Edmondson grade, tumor capsule, tumorpathology, endoscopic vascular invasion, p27and nm23, CK19and Survivin protein,E-cadherin and MMP-9, HIF-1α and p53are risk factors for early postoperativerecurrence and metastasis of small hepatocellular carcinoma(P＜0.05); multivariatelogistic regression analysis revealed that tumor size, tumor capsule, CK19, nm23andE-cadherin protein are independent risk factors of small hepatocellular carcinoma inpatients with early postoperative recurrence and metastasis(P＜0.05).Conclusion1. Tumor size, Edmondson grade, tumor capsule, tumor pathology, endoscopicvascular invasion, p27and nm23, CK19and Survivin protein, E-cadherin and MMP-9,HIF-1α and p53are risk factors for early postoperative recurrence and metastasis ofsmall hepatocellular carcinoma; tumor size, tumor capsule, CK19, nm23andE-cadherin protein are independent risk factors of small hepatocellular carcinoma inpatients with early postoperative recurrence and metastasis, they may be used as abasis for the assessment of early recurrence and metastasis of small hepatocellularcarcinoma after curative hepatic resection.2. To establish a multi-factor, multi-protein mathematical prediction model ofearly postoperative recurrence and metastasis of small hepatocellular carcinoma isinitially formed an individual prediction system, which may be used to screen initiallyhigh-risk patients of early postoperative recurrence and metastasis.