Dechaphunkul Arunee, Phukaoloun Monlika, Kanjanapradit Kanet, Graham Kathryn, Ghosh Sunita, Santos Cheryl, Mackey John R
Department of Oncology, Cross Cancer Institute, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada T6G 1Z2 ; Holistic Center for Cancer study and Care (HOCC-PSU) and Division of Medical Oncology, Department of Internal Medicine, Prince of Songkla University, Songkhla, Thailand.
Int J Breast Cancer. 2012;2012:290854. doi: 10.1155/2012/290854. Epub 2012 Sep 4.
Introduction. Despite advances in breast cancer systemic treatment, new prognostic and predictive factors are still needed. Tissue inhibitor of metalloproteinase-1 (TIMP-1), a physiologic inhibitor of matrix metalloproteinases (MMPs), can act in both pro- and antitumoral effects. As role of TIMP-1 in breast cancer is controversial, we aimed to determine the prognostic significance of TIMP-1 in breast cancer. Methods. A single center-based case-control study was applied. Primary breast cancers from women with early stage disease treated with standard adjuvant therapy were analyzed by gene expression microarrays and immunohistochemistry for TIMP-1. Results. At the optimized cut-point, patients with high TIMP-1 RNA levels had a significantly shorter time to relapse, with a hazard ratio (HR) of 1.64 (P = 0.04), but without significant differences in overall survival (HR 1.29, P = 0.37). Although cytoplasmic overexpression of TIMP-1 protein was not correlated with early relapse (HR 1.0, P = 0.92), there was a tendency for short overall survival in patients with high expression (HR 1.41, P = 0.21). Conclusions. Our data indicate that elevated TIMP-1 RNA levels are independently prognostic for early recurrence, and there is a tendency for association of high cytoplasmic TIMP-1 protein levels with short survival in primary breast cancer.
引言。尽管乳腺癌全身治疗取得了进展，但仍需要新的预后和预测因素。金属蛋白酶组织抑制剂-1（TIMP-1）是基质金属蛋白酶（MMPs）的生理性抑制剂，可发挥促肿瘤和抗肿瘤作用。由于TIMP-1在乳腺癌中的作用存在争议，我们旨在确定TIMP-1在乳腺癌中的预后意义。方法。应用一项基于单中心的病例对照研究。对接受标准辅助治疗的早期疾病女性的原发性乳腺癌进行基因表达微阵列分析和TIMP-1免疫组织化学分析。结果。在优化的切点处，TIMP-1 RNA水平高的患者复发时间显著缩短，风险比（HR）为1.64（P = 0.04），但总生存期无显著差异（HR 1.29，P = 0.37）。尽管TIMP-1蛋白的细胞质过表达与早期复发无关（HR 1.0，P = 0.92），但高表达患者的总生存期有缩短的趋势（HR 1.41，P = 0.21）。结论。我们的数据表明，TIMP-1 RNA水平升高是早期复发的独立预后因素，原发性乳腺癌中细胞质TIMP-1蛋白水平高与生存期短存在关联趋势。
