肺癌组织中凝血、纤溶成分过度表达对非小细胞肺癌预后的影响

Influence of overexpressed coagulantic and fibrolytic components in tumor tissues on the prognosis of non-small cell lung cancer

目的探讨凝血系统成分组织因子(TF)、纤溶系统成分尿激酶型纤溶酶原激活物(uPA),尿激酶型纤溶酶原激活物受体(uPAR)在非小细胞肺癌(NSCLC)组织中的表达及其与NSCLC 微血管密度(MVD)、淋巴结转移、血管浸润及预后之间的关系。方法采用免疫组织化学方法检测97例 NSCLC 组织和40例癌旁正常肺组织中 TF、uPA 及 uPAR 的表达。采用 t 检验、x^2检验和 Kaplan-Meier 生存曲线分析 TF、uPA、uPAR 表达与 MVD、淋巴结转移、血管浸润及预后之间的关系。结果 TF、uPA 和 uPAR 在 NSCLC 组织中广泛表达,阳性率分别为61.9%、58.8%和61.9%。癌旁正常肺组织中仅有少量巨噬细胞、纤维母细胞呈弱阳性表达。TF(34/47)、uPA(33/47)及 uPAR(39/47)表达均与淋巴结转移相关(x^2值分别为4.248、4.933、17.243,均 P<0.05)。TF 阳性绀和阴性组 MVD 值分别为1.50+0.19和1.37+0.16,TF 表达与 MVD 相关(P<0.01),uPAR 表达(35/44)与血管浸润相关(x^2=10.680,P<0.01)。TF 与 uPAR 表达有一致性(r=0.432,P<0.01)。TF 与uPAR 协同表达与淋巴结转移和血管浸润均明显相关(P<0.01)。TF、uPAR 及 TF-uPAR 阳性表达组患者中位生存时间较阴性组患者明显缩短。结论 TF 促进肿瘤微血管形成,uPAR 表达与淋巴结转移、血管浸润相关,二者协同表达可能影响 NSCLC 患者预后。

Objective To evaluate the expression of tissue factor （TF）, urokinase-type plasminogen activator （uPA）, and urokinase-type plasminogen activator receptor （uPAR） in non-small cell lung cancer （NSCLC） tissues and to find their roles in lymph node metastasis, vascular involvement and prognosis. Methods Immunohistochemistry was used to examine the expression of TF, uPA, and uPAR in the tumor tissues of 97 NSCLC patients obtained during operation and 40 samples of normal lung tissues at least 5 cm away from the tumor tissues. The correlations of expression of TF, uPA, and uPAR with the clinicopathologic parameters were analyzed by X^2 test. The survival rates were calculated by Kaplan-Meier method. Results TF, uPA, and uPAR were diffusely expressed in the carcinoma cell cytoplasm with the positive rates of 61.9%, 58.8%, and 61.9% respectively; however, they were only weakly expressed in the scattered macrophage and fibroblast cells in the normal lung tissues. TF expression was correlated with tumor angiogenesis as measured by microvessel density （P 〈0.01 ） ; TF（34/47） , uPA（33/47） , and uPAR （ 39/47 ） expressions were all positively correlated with lymph node metastasis （ P 〈 0.05, P 〈 0.05, and P 〈 0.01 ）, and the uPAR expression was positively correlated with vascular involvement （ P 〈 0.01 ）. The agreement between TF and uPAR expression was significant （r = 0. 432,P 〈 0.01 ）. Co-expression of TF and uPAR was significantly correlated with lymph node metastasis and vascular involvement. Kaplan-Meier survival analysis showed that median the survival time of the patients with TF,uPAR and TF-uPAR positive tumor was shorter than that of the patients with TF, uPAR and TF-uPAR negative tumors （P 〈 0.01 ）. Conclusion TF promotes angiogenesis, and uPAR contributes to lymph node metastasis and vascular involvement. Coexpression of TF and uPAR may play an important role in the metastasis and prognosis of NSCLC.