基质金属蛋白酶-9及其组织抑制物-1在皮肤鳞状细胞癌中的表达

Expression of Matrix Metalloproteinase-9 and Its Tissue Inhibitor in Cutaneous Squamous Cell Carcinoma

目的探讨基质金属蛋白酶-9(MMP-9)及其组织抑制物-1(TIMP-1)在皮肤鳞状细胞癌(SCC)中的表达及其与肿瘤浸润转移的关系。方法免疫组化SP法检测MMP-9和TIMP-1蛋白在65例皮肤SCC(Bowen病17例,SCC48例)和5例正常表皮石蜡切片的表达,采用图像分析技术对免疫组化结果进行定量分析。结果MMP-9和TIMP-1蛋白均弥漫表达于皮肤SCC,分布于SCC癌巢及癌巢周围间质细胞,而在正常人皮肤仅见MMP-9和TIMP-1的弱阳性表达。SCC组MMP-9蛋白的表达水平及MMP-9/TIMP1比值高于Bowen病组(t值分别为2.33、2.36,P<0.05),SCC中淋巴结转移组MMP-9/TIMP1的比值高于无淋巴结转移组(t=2.46,P<0.05)。结论MMP-9、TIMP-1蛋白的表达与SCC的侵袭性有关,MMP-9/TIMP1比值升高(MMP-TIMP失衡)预示了SCC肿瘤细胞较高的侵袭转移潜能。

Objectives To investigate the expression of matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor (TIMP-1) in cutaneous squamous cell carcinomas (SCC) and the relationship between the expression and invasive growth and metastasis of SCC. Methods Immunohistochemical method of streptavidin-peroxidase (SP) was used to detect the expression of MMP-9 and TIMP-1 proteins on the paraffin embedded sections of 65 patients with cutaneous SCC and 5 cases of normal epidermis. The immunohistochemical results were analyzed quantitatively using an image analysis system. Results MMP-9 and TIMP-1 proteins were diffusely expressed on the tumor nests and the mesenchymal cells around the nests, while in normal epidermis MMP-9 and TIMP-1 were weakly positive. The expression level of MMP-9 protein and the ratio of MMP-9/TIMP-1 were higher in aggressive SCC group than those SCC in situ group (t = 2.33 and 2.36, respectively, P < 0.05). The ratio of MMP-9/TIMP-1 was higher in the patients with positive lymph node metastasis than in the negative group(t = 2.46, P < 0.05). Conclusions The expression level of MMP-9 and TIMP-1 protein correlates with the aggressive behavior of cutaneous SCC and the higher ratio of MMP-9/TIMP1 (the imbalance between MMP and TIMP) may indicate a higher risk of the tumor invasion and metastasis.