血管生成拟态和基质金属蛋白酶-2在前列腺癌中的表达及意义

Expression and significance of vasculogenic mimicry and matrix metalloproteinase-2 in prostate cancer

目的研究血管生成拟态（vasculogenic mimicry，VM）在人前列腺癌组织中的分布及与预后的关系，探讨基质金属蛋白酶-2（matrix metalloproteinase-2，MMP-2）在前列腺癌VM形成中的作用。方法选取天津医科大学第二医院1995年1月至2008年12月收治的前列腺癌患者96例。年龄59～72岁，平均（66．7±11．0）岁。术前血清PSA为15．6—76．7μg／L，平均（34．6±1．7）μg／L。术前经MRI检查及穿刺活检均诊断为局灶性前列腺癌。收集前列腺根治性切除术后的组织标本，采用血小板-内皮细胞黏附分子-1（platelet—endothelial cell adhesion molecule-1，PECAM-1／CD31）免疫组化和过碘酸雪夫氏（periodicacid．sciff，PAS）组织化学双重染色后，光镜下观察VM结构，比较VM表达阳性组和阴性组的预后情况，分析VM表达与预后的关系。免疫组化法检测MMP-2在前列腺癌组织中的表达，分析MMP-2蛋白表达与VM形成的关系和作用。结果96例中24例存在VM结构，VM阳性组平均Gleason评分8．0±0．3，PSA（37．7±2．3）μg／L，均高于VM阴性组Gleason评分6．2±0．3，PSA（19．5±2．1）μg／L，差异有统计学意义（P〈0．05）。VM阴性组无生化复发中位生存期96个月，高于VM阳性组无生化复发中位生存期39个月，差异有统计学意义（P〈0．05）。MMP-2表达和VM的形成呈明显正相关（r2=0．60，P〈0．01）。结论前列腺癌组织中VM形成与组织恶性程度相关，肿瘤细胞分泌MMP，2可能促进了VM的形成，VM阳性和MMP-2高表达与前列腺癌预后不良有关。

Objective To find out if an unique blood mode-vasculogenic mimicry （VM） exist in prostate cancer and analyze its relationship with prognosis. Methods The age of the patients was 59 to 72 years, with a mean age of （66.7 ＋ 11.0） years. All had been confirmed as prostate cancer by biopsy. The level of serum PSA was 15.6 to 76.7 μg/L, with a mean level of （34.6 ＋ 1.7） μg/L. A histochemical and immunohistochemical dual staining method for PAS-CD31 and MMP-2 in 96 prostatic adenocarcinomas were conducted to explore if VM exist in prostate cancer, describe its morphology and distribution. The different expression of MMP-2 in VM positive and VM negative tissue were. The clinical data were collected and ana- lyzed to explore the relationship between disease progression and VM. Results Among 96 cases, 24 cases were found VM positive, the others were negative. The boundary membrane of VM was PAS positive, which was continuous or incontinuous. A positive correlation between VM density and high Gleason score were found. The tPSA were higher in the VM positive cases than that in VM negatives. The VM positive patients had poorer prognosis than that of the negatives. The MMP-2 expression was found correlated with VM posi- tive （re = 0.60, P 〈 0.01 ）. Conclusions VM exists in the prostate cancer as an independent structure, and it is more common in the high-grade cancer. The progression-free survival of VM positive patients could be worse than the negative. MMP-2 and VM could be the indicators of poor prognosis.