Ree A H, Florenes V A, Berg J P, Maelandsmo G M, Nesland J M, Fodstad O
Departments of Tumor Biology and Pathology, The Norwegian Radium Hospital, and Hormone Laboratory, Aker Hospital, University of Oslo, Oslo, Norway.
Clin Cancer Res. 1997 Sep;3(9):1623-8.
Tissue inhibitors of metalloproteinases (TIMPs) are believed to possess several cellular functions, particularly the contrasting activities of inhibiting tissue-degrading enzymes and promoting cellular growth. In attempts to elucidate which of these functions may prevail in breast cancer, expression of mRNAs for TIMP-1 and TIMP-2 in the primary carcinomas from 34 breast cancer patients was related to known prognostic parameters and the clinical outcome. High levels of TIMP-1 mRNA showed significant correlation with the presence of lymph node metastases (P = 0.0067), development of distant metastases (P = 0.014), and early death of the disease (P = 0.020). Elevated expression of TIMP-2 mRNA was associated with development of distant metastases (P = 0.0055). No correlations, however, were observed between mRNA levels of TIMPs and prognostic factors such as patient age, tumor size, grade of anaplasia, or steroid receptor status; neither were any correlations found between these clinicopathological characteristics and the mRNA expression of the collagenolytic enzymes matrix metalloproteinase-2 and matrix metalloproteinase-9. The present data suggest that high levels of TIMP-1 and TIMP-2 mRNAs in the primary carcinomas are strongly associated with development of metastasis in breast cancer.
金属蛋白酶组织抑制剂（TIMPs）被认为具有多种细胞功能，尤其是在抑制组织降解酶和促进细胞生长这两种相反的活性方面。为了阐明这些功能中哪一种在乳腺癌中可能占主导地位，对34例乳腺癌患者原发癌中TIMP - 1和TIMP - 2的mRNA表达与已知的预后参数及临床结果进行了关联研究。高水平的TIMP - 1 mRNA与淋巴结转移的存在（P = 0.0067）、远处转移的发生（P = 0.014）以及疾病的早期死亡（P = 0.020）显著相关。TIMP - 2 mRNA的表达升高与远处转移的发生相关（P = 0.0055）。然而，未观察到TIMPs的mRNA水平与患者年龄、肿瘤大小、间变程度或类固醇受体状态等预后因素之间存在相关性；在这些临床病理特征与胶原分解酶基质金属蛋白酶 - 2和基质金属蛋白酶 - 9的mRNA表达之间也未发现任何相关性。目前的数据表明，原发癌中高水平的TIMP - 1和TIMP - 2 mRNA与乳腺癌转移的发生密切相关。
