金属蛋白酶组织抑制物与乳腺癌转移及预后的关系

Relationship between tissue inhibitors of metalloproteinase and metastasis and prognosis in breast cancer

目的 探讨金属蛋白酶组织抑制物 (tissueinhibitorsofmetalloproteinases ,TIMP) 3和 4在乳腺癌患者病程进展中的临床意义。 方法 对 70例原发性乳腺癌患者癌组织石蜡标本 ,采用原位杂交法检测TIMP 3、TIMP 4mRNA的表达水平 ;采用标准链霉菌抗生物素蛋白 过氧化物酶亲合免疫组化法检测肿瘤组织微血管密度 (MVD)和血管内皮生长因子 (VEGF)水平 ,并根据患者腋淋巴结转移状况和生存率进行对比研究。 结果 本组患者无腋淋巴结转移组的TIMP 3和TIMP 4mRNA表达水平高于有腋淋巴结转移组 ,差异有显著性意义 (P <0 0 1) ;单因素分析表明 ,随着癌组织TIMP 3和TIMP 4mRNA表达水平增高 ,患者生存期延长 (P <0 0 1)。进一步将癌组织的腋淋巴结转移状态、TNM分期、MVD及VEGF表达水平等因子引入Cox比例风险模型分析 ,显示TIMP 3、TNM分期及MVD3项为影响预后的主要因素。 结论 TIMP 3和TIMP 4mRNA表达水平与乳腺癌患者的转移和预后相关 ,其中TIMP 3对患者预后具有独立的意义。

Objective To investigate the clinical significance of tissue inhibitors of metalloproteinase (TIMP) 3 and TIMP 4 in human breast cancer. [WT5”HZ]Methods The levels of TIMP 3 and TIMP 4 mRNA in paraffin embedded breast carcinoma specimens from 70 patients with primary invasive breast cancer who had undergone radical mastectomy from January of 1984 to December of 1985 were assessed by in situ hybridization assay. Intratumoral microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression were detected by tho standard streptavidin biotin peroxides method. [WT5”HZ]Results Both TIMP 3 and TIMP 4 mRNA expressions were higher in patients with axillary lymph node metastasis than in those without metastasis ( P <0 01), and patients with higher expression of any of these two genes had a better prognosis than those with lower expression ( P <0 01). We introduced lymph node status, TNM staging, MVD and VEGF expression, plus TIMP 3 and TIMP 4 to the Cox′s proportional hazards regression model for significant analysis, and found that the TIMP 3, TNM staging and MVD play an important role in prognosis of this group. [Conclusions TIMP 3 and TIMP 4 are correlated with metastasis in breast cancer, and TIMP 3 demonstrates an independent prognostic factor for the patients. These results provide a valuable clue for developing new, practical prognosticators in breast cancer patients.