Wu Zheng-Sheng, Wu Qiang, Yang Jiu-Hua, Wang Hong-Qun, Ding Xiang-Dong, Yang Feng, Xu Xiao-Chun
Department of Pathology, Anhui Medical University, Hefei, Anhui, People's Republic of China.
Int J Cancer. 2008 May 1;122(9):2050-6. doi: 10.1002/ijc.23337.
Tumor progression and metastasis contribute to the great majority of breast cancer deaths. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are thought to be involved in tumor progression and metastasis. Thus, we determined whether the expression of MMP-9 and TIMP-1 is associated with prognosis in breast cancer patients. We measured serum MMP-9 and TIMP-1 by enzyme-linked immunosorbent assay in 60 breast cancer patients, 18 benign breast disease patients and 15 healthy controls. We also evaluated the expression of MMP-9 and TIMP-1 protein and mRNA in paraffin-embedded tumor tissues from the 60 breast cancer patients by immunohistochemistry and in situ hybridization. We then correlated serum and tissue levels of MMP-9 and TIMP-1 in breast cancer samples and their expression with patients' clinicopathologic characteristics. We found that serum levels of MMP-9 and TIMP-1 were significantly higher in breast cancer patients than in benign breast disease and in healthy controls. High serum levels of MMP-9 and TIMP-1 were associated with lymph node metastasis, higher tumor stage and lower relapse-free and overall survival (OS) rates. Compared to low expression, high tissue expression of MMP-9 protein was associated with lymph node metastasis and higher tumor stage; and high tissue expression of TIMP-1 was associated with a lower OS rate. Our findings suggest that MMP-9 and TIMP-1 may further be evaluated as biomarkers for predicting progression and prognosis of breast cancer.
肿瘤进展和转移是导致大多数乳腺癌患者死亡的原因。基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）被认为与肿瘤进展和转移有关。因此，我们确定MMP-9和TIMP-1的表达是否与乳腺癌患者的预后相关。我们采用酶联免疫吸附测定法测量了60例乳腺癌患者、18例乳腺良性疾病患者和15例健康对照者血清中的MMP-9和TIMP-1。我们还通过免疫组织化学和原位杂交评估了60例乳腺癌患者石蜡包埋肿瘤组织中MMP-9和TIMP-1蛋白及mRNA的表达。然后，我们将乳腺癌样本中MMP-9和TIMP-1的血清和组织水平及其表达与患者的临床病理特征进行了关联分析。我们发现，乳腺癌患者血清中MMP-9和TIMP-1水平显著高于乳腺良性疾病患者和健康对照者。血清中MMP-9和TIMP-1水平升高与淋巴结转移、更高的肿瘤分期以及更低的无复发生存率和总生存率（OS）相关。与低表达相比，MMP-9蛋白的高组织表达与淋巴结转移和更高的肿瘤分期相关；TIMP-1的高组织表达与更低的OS率相关。我们的研究结果表明，MMP-9和TIMP-1可能进一步作为预测乳腺癌进展和预后的生物标志物进行评估。
