尿激酶型纤溶酶原激活物及其特异受体和抑制物与肝细胞癌浸润转移及预后

Urokinase type plasminogen activator (uPA), uPA receptor (uPA R) and inhibitors (PAⅠ 1) expression in hepatocellular carcinoma in relation to cancer invasion/metastasis and prognosis

目的研究尿激酶型纤溶酶原激活物（ｕＰＡ）及其特异受体（ｕＰＡ－Ｒ）和抑制物（ＰＡⅠ－１）与肝细胞癌（ＨＣＣ）的关系及其在ＨＣＣ浸润转移中的作用。方法用ｕＰＡ、ＰＡⅠ－１单克隆抗体和ｕＰＡ－Ｒ多抗分别检测ｕＰＡ、ＰＡⅠ－１和ｕＰＡ－Ｒ在４８例ＨＣＣ和１２例对照组中蛋白水平的表达。结果癌与癌周及对照组比较，ｕＰＡ、ｕＰＡ－Ｒ和ＰＡⅠ－１膜上免疫染色阳性率明显升高，Ｐ＜０．０５。在侵袭性病例中，ｕＰＡ和ｕＰＡ－Ｒ阳性为１６／２２和１９／２２，与非侵袭性７／２６和１０／２６相比，Ｐ分别＜０．０１和＜０．００１。癌栓形成和淋巴结转移病例ｕＰＡ－Ｒ阳性分别为８／８和６／６。术后复发病例ｕＰＡ－Ｒ阳性为１５／１７，与无复发组１４／３１相比，Ｐ＜０．０１。术后２年死亡患者ｕＰＡ－Ｒ和ＰＡⅠ－１阳性分别为１２／１２和９／１２，与生存组１７／３６和１５／３６相比，Ｐ分别＜０．０１和＜０．０５。在ｕＰＡ、ｕＰＡ－Ｒ和ＰＡⅠ－１同时阳性病例中，侵袭性肿瘤和术后２年死亡分别占１１／１５和７／１５，与阴性组２／８和０／８相比，Ｐ＜０．０５。结论ｕＰＡ、ｕＰＡ－Ｒ和ＰＡⅠ－１在ＨＣＣ中表达明显升高，ｕＰＡ和ｕＰＡ－Ｒ与ＨＣＣ浸润转移密切?

Objective To study the relevance of uPA, uPA R and PAⅠ 1 to hepatocellular cancer (HCC). Methods The expression at protein level for uPA, uPA R and PAⅠ 1 was examined in 48 cases of HCC and 12 cases of benign tumors of the liver (as control) immunohistochemically.Results When compared to HCC adjacent normal liver tissue and the control, positive rates of immune staining for uPA, uPA R and PAⅠ 1 on cell membrane were significantly higher in HCC cells ( P <0.05). Posi tive staining of uPA and uPA R was seen in 16 of 22 and 19 of 22 cases of HCC with invasion, respectively ( P <0.01 and <0.001). In 8 of 8 cases with cancer emboli, and in 6 of 6 cases with lymph node metastasis was the expression of uPA R positive. Compared with 2 of 17 cases without recurrence, uPA R was positive in 15 of 17 recurrent cases ( P <0.01). In 36 cases who survived, 17 was positive for uPA R and 15 for PAⅠ 1, while in 12 cases who died 2 years after surgery, 12 and 9 cases were positive for uPA R and PAⅠ 1, respectively ( P <0.01 and <0.05). In 15 cases positive for all three parameters, 11 had cancer invasion and 7 died in 2 years, while in the controls with negative staining 2 had invasion and none died in 2 years ( P <0.05).Conclusion Expression of uPA, uPA R and PAⅠ 1 is increased in HCC, and uPA and uPA R may contribute significantly to HCC invasion and metastasis. uPA R and PAⅠ 1 are associated with poor prognosis.