Yamamura Tsuyoshi, Nakanishi Kuniaki, Hiroi Sadayuki, Kumaki Fumiyuki, Sato Hiroshi, Aida Shinsuke, Kawai Toshiaki
Department of Pathology, National Defense Medical College, Tokorozawa 359-8513, Japan.
Lung Cancer. 2002 Mar;35(3):249-55. doi: 10.1016/s0169-5002(01)00431-7.
For the metastasis and invasion of cancer cells, destruction of extracellular matrix is essential. In this process, collagen is broken down by some matrix metalloproteinases. Matrix metalloproteinase 2 (MMP2) is able to cleave type IV collagen, and membrane-type-1-matrix metalloproteinase (MT1-MMP) induces activation of proMMP2. We investigated the expressions of MT1-MMP and MMP2 and their relation to both clinicopathologic parameters and clinical outcome in non-small cell lung carcinomas (NSCLC). Eighty-nine specimens of NSCLC were examined using in situ hybridization and immunohistochemistry. Each metalloproteinase was expressed within the cytoplasm of tumor cells with or without stromal cells in NSCLC. Tumors in which tumor cells strongly stained for MT1-MMP mRNA or protein made up more than 50% of the tumor area were found in 44 and 26% of cases, respectively. The corresponding values for MMP-2 mRNA and protein, were 51 and 26%. Our analysis of clinicopathological findings revealed a significant positive relationship between MT1-MMP mRNA and p-M. The correlation between MMP2 protein-staining status and overall survival rate reached significance in the univariate analysis. However, an association was not demonstrated in the multivariate analysis. The detection of MT1-MMP and MMP2 is likely to be of limited value in informing the prognosis in NSCLC.
对于癌细胞的转移和侵袭而言,细胞外基质的破坏至关重要。在此过程中,胶原蛋白会被一些基质金属蛋白酶分解。基质金属蛋白酶2(MMP2)能够切割IV型胶原蛋白,而膜型1基质金属蛋白酶(MT1-MMP)可诱导前MMP2的激活。我们研究了MT1-MMP和MMP2的表达及其与非小细胞肺癌(NSCLC)临床病理参数和临床结局的关系。使用原位杂交和免疫组织化学方法检测了89例NSCLC标本。在NSCLC中,每种金属蛋白酶在肿瘤细胞的细胞质中表达,无论有无基质细胞。分别在44%和26%的病例中发现,MT1-MMP mRNA或蛋白强染色的肿瘤细胞占肿瘤面积的50%以上。MMP-2 mRNA和蛋白的相应值分别为51%和26%。我们对临床病理结果的分析显示,MT1-MMP mRNA与p-M之间存在显著正相关。在单变量分析中,MMP2蛋白染色状态与总生存率之间的相关性具有统计学意义。然而,在多变量分析中未显示出相关性。MT1-MMP和MMP2的检测在预测NSCLC预后方面可能价值有限。