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目的探讨MMP-1,-2,-9,-14表达与胆囊癌患者的预后和有/无血管生成拟态的相关性。方法免疫组化染色(IHC)计算机图像定量分析、高/低免疫反应性截点得分选择和ROC曲线被用来分析基质金属蛋白酶(MMP,2,9,和14)在89例胆囊癌(GBC)表达及其与血管生成拟态(VM)和临床病理特征、预后的相关性。结果 MMP-2与MMP-14(MT1-MMP)表达明显与胆囊癌VM相关(P均<0.01),与Nevin分期、分化和无VM组肝转移程度相关(P均<0.05);此外,MMP-2表达也与浆膜浸润和VM组肝转移相关(P均<0.05)。在胆囊癌VM患者中,MMP-2表达与临床病理参数如中度分化、Nevin分期(S3-S5)、肝转移、浆膜浸润和淋巴结转移相关(P<0.05),MMP-14表达与分化程度(G2和G3)、Nevin分期、淋巴结转移、浆膜侵犯、阴性肝转移和浆膜浸润相关(P均<0.05)。多变量分析显示,MMP-2与MMP-14为胆囊癌VM阴性或阳性患者总生存和不良预后的独立因素(P均<0.05)。结论 MMP-2、MMP-14是有/无VM胆囊癌患者的独立的预后因素,在VM形成和GBC进展中可能起重要作用。
Objective To investigate the relationship between the expression of MMP-1, -2, -9, -14 and prognosis and / or angiogenic mimicry in patients with gallbladder cancer. Methods Immunohistochemical (IHC) computer image quantitative analysis, high / low immunoreactive intercept score selection and ROC curves were used to analyze the association between matrix metalloproteinases (MMPs, 2,9, and 14) in 89 gallbladder carcinomas (GBC ) Expression and its relationship with vasculogenic mimicry (VM), clinicopathological features and prognosis. Results The expressions of MMP-2 and MMP-14 (MT1-MMP) were significantly correlated with VM in gallbladder carcinoma (all P <0.01), and were correlated with Nevin staging, differentiation and VM-free liver metastasis (all P <0.05) -2 expression was also associated with serosal invasion and VM group liver metastasis (all P <0.05). In patients with gallbladder carcinoma, the expression of MMP-2 was correlated with clinicopathological parameters such as moderate differentiation, Nevin staging (S3-S5), hepatic metastasis, serosal invasion and lymph node metastasis (P <0.05) (G2 and G3), Nevin stage, lymph node metastasis, serosal invasion, negative liver metastasis and serosal invasion (all P <0.05). Multivariate analysis showed that MMP-2 and MMP-14 were independent prognostic factors for overall survival and poor prognosis in patients with negative or positive gallbladder carcinoma (all P <0.05). Conclusion MMP-2 and MMP-14 are independent prognostic factors in patients with and without VM gallbladder carcinoma and may play an important role in VM formation and GBC progression.