肝细胞肝癌组织表达IL-8对肿瘤侵袭、转移的影响

Expression of IL-8 in hepatocellular carcinoma and its clinicopathological significance

目的探讨评估肝细胞肝癌(hepatocellular carcinoma,HCC)组织中白细胞介素8(interleukin-8,IL-8)的表达及其对HCC侵袭、转移的影响。方法随机选取100例经部分肝切除术治疗的HCC患者石蜡组织切片标本,同时收集患者的临床病理资料。利用免疫组织化学方法分别检测IL-8、VEGF、基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)、分化抗原群68(cluster of differentiation 68,CD68)、CD163、CD31等炎性反应指标,Ecadherin、β-catenin等上皮间质转化(epithelial-mesenchymal transition,EMT)指标的表达。分析IL-8与临床病理指标的相关性。结果在HCC标本中,IL-8高表达(IL-8high)标本占50.0%(50/100),其炎性反应指标的阳性率高于IL-8低表达(IL-8low)标本:VEGF(52.5%vs 32.5%,P=0.026),MMP-9(50.3%vs 22.5%,P=0.030)。IL-8high标本中M2型肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)及微血管密度高于IL-8low标本(53.62±9.24 vs32.72±10.34,P<0.001;34.00±16.57 vs 26.94±14.38,P<0.001)。IL-8high标本中E-cadherin表达减少(5.0%vs15.0%,P=0.041),β-catenin在细胞质内积聚(17.5%vs 5.0%,P=0.047)。IL-8表达与肿瘤包膜、门静脉癌栓浸润相关(P=0.031,P=0.027)。结论在HCC组织内IL-8呈高表达,与炎性相关分子和EMT分子的表达高度相关,并与HCC侵袭、转移有关。

Objective To investigate the expression of interleukin-8（IL-8） in hepatocellular carcinoma（HCC） and its clinicopathological significance.Methods The expression of IL-8,epithelial-mesenchymal transition（EMT）-related proteins（E-cadherin,β-catenin） and inflammation markers including VEGF,matrix metalloproteinase-9（MMP-9）,cluster differentiation 68（CD68）,CD163 and CD31 were examined in 100 paraffin-embedded HCC samples with immunohistochemistry.The correlation of the expression of these proteins with clinical and pathological indicators was analyzed.Results The rate of high IL-8 expression（IL-8high） was 50.0%（50/100） in HCC samples.The positive rates of VEGF and MMP-9 in IL-8highsamples were significantly higher than those in low IL-8 expression（IL-8low） samples（52.5% vs 32.5%,P = 0.026;50.3% vs 22.5%,P = 0.030,respectively）,and type M2 tumor-associated macrophages（M2 TAMs） and micro-vessel density（MVD） were also higher（53.62 ± 9.24 vs 32.72 ± 10.34,P 〈 0.001;34.00 ±16.57 vs 26.94 ± 14.38,P 〈 0.001,respectively）.The expression of E-cadherin was decreased（5.0% vs 15.0%,P =0.041） and β-catenin was translocated to cytoplasm（17.5% vs 5.0%,P = 0.047） in IL-8highsamples.IL-8 expression was correlated with envelope and portal vein invasion（P = 0.031,P = 0.027） of HCC patients.Conclusion High expression of IL-8 in HCC tissue is correlated with inflammation and EMT and also associated with invasion and metastasis of HCC.