凋亡及血管生成因子在肝细胞肝癌中的表达及意义

Expression and clinical significance of certain apoptosis and angiogenesis factors in hepatocellular carcinoma

目的研究部分凋亡及血管生成因子在肝细胞肝癌(肝癌)中的表达及其临床意义。方法应用免疫组化方法检测90例肝癌标本中p53、Survivin、基质金属蛋白酶(MMP)-2、MMP-9及血管内皮生长因子(VEGF)的表达情况,并分析其与肝癌术后复发的关系。结果p53、Survivin、MMP-2、MMP-9及VEGF的阳性率分别为33·3%、51·1%、60·0%、37·8%及76·7%。经相关性分析,VEGF与MMP-2、VEGF与MMP-9的表达呈正相关;MMP-2、MMP-9及VEGF与术后复发呈正相关(P<0·05)。MMP-2阴性组的1、2、3年无瘤生存率分别显著高于MMP-2阳性组中的相应指标(P<0·05),MMP-9和VEGF中亦发现类似结果。多因素分析发现术前播散结节、镜下微转移灶、血清甲胎蛋白水平以及VEGF和MMP-9的表达水平是肝癌术后复发的独立危险因素。结论p53和Survivin与肝癌术后复发无关;MMPs和VEGF与肝癌术后复发相关,可用于评价术后复发风险。

Objective To investigate the expression and clinical significance of some apoptosis and angiogenesis factors in hepatocellular carcinoma （ HCC ）. Methods The expression of p53, Survivin, matrix metalloproteinases（MMP） -2, MMP-9 and vascular endothelial growth factor（VEGF） in 90 specimens of HCC was detected by immunohistochemistry. Correlations of the factors to the recurrence of HCC after hepatectomy were analyzed. Results The positive rate of p53, Survivin, MMP-2, MMP-9 and VEGF in HCC tissue was 33.3%, 51.1%, 60.0%, 37.8% and 76. 7%, respectively. Of the 5 factors, positive correlation only occurred between the expression of MMP-2 and VEGF, MMP-9 and VEGF. The expression of MMP-2, MMP-9 and VEGF was correlated to the recurrence of HCC. The 1-, 2-, and 3-year tumor-free survival rates were significantly higher in MMP-2 （ - ） group than in MMP-2 （ ＋ ） group, and the same results were found with MMP-9 and VEGF. Multivariate analysis revealed that macroscopically disseminated nodules, tumor micrometastasis, serum alpha fetal protein （AFP） level, the expression of MMP-9 and VEGF were independent recurrence risk factors in HCC. Conclusions Neither p53 nor Survivin is correlated to the recurrence of HCC; MMPs and VEGF are correlated to the recurrence, and can be used to estimate the risk of postoperative recurrence of HCC.