The clinical relevance of stromal matrix metalloproteinase expression in ovarian cancer (Publication with Expression of Concern)
The clinical relevance of stromal matrix metalloproteinase expression in ovarian cancer (Publication with Expression of Concern)
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DOI：
10.1158/1078-0432.ccr-05-2338
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发表时间：
2006-03-15
影响因子：
11.5
通讯作者：
Sood, AK
中科院分区：
文献类型：
--
作者：
Kamat, AA;Fletcher, M;Sood, AK
目的：基质金属蛋白酶（MMP）是一种蛋白水解酶，与肿瘤的进展和转移有关。我们试图确定MMPs的上皮（肿瘤细胞衍生的）和基质（宿主衍生的）表达在预测上皮性卵巢癌（EOC）患者的临床结果中的作用。实验设计：使用免疫组织化学在90个侵袭性EOC中评估MMP-2、MMP-9和膜1型（MT 1）-MMP表达，并对样本的上皮和基质染色进行评分。结果：MMP-2、MMP-9和MT 1-MMP在肿瘤上皮中的高表达率分别为54%、97%和100%，在间质中的高表达率分别为38%、70%和38%。基质中MMP-2、MMP-9和MT 1-MMP的高表达与高分期、高级别腹水和阳性淋巴结状态等侵袭性特征显着相关。Kaplan-Meier分析显示，MMP-2、MMP-9和MT 1-MMP的高上皮和间质表达均与较短的疾病特异性生存期显著相关（DSS; P < 0.01）。在树状结构生存分析中，上皮MT 1-MMP强表达的患者的DSS最短，而上皮MT 1-MMP中度表达和间质MMP-9低表达的患者的DSS最长（P < 0.01）。多因素分析显示，MMP-9（P = 0.01）和MT 1-MMP（P = 0.04）高表达、上皮细胞MT 1-MMP（P = 0.01）高表达和高分期（P = 0.04）是上皮性卵巢癌预后不良的独立预测因子。因此，宿主来源的MMPs是EOC临床结果的有价值的预测因子。
Purpose: Matrix metalloproteinases (MMP) are proteolytic enzymes implicated in cancer progression and metastasis. We sought to determine the role of epithelial (tumor cell - derived) and stromal (host-derived) expression of MMPs in predicting the clinical outcome of patients with epithelial ovarian cancer (EOC).Experimental Design: MMP-2, MMP-9, and membrane type 1 (MT1)-MMP expression was evaluated using immunohistochemistry in 90 invasive EOCs, and samples were scored for epithelial and stromal staining. Results were correlated with clinicopathologic characteristics using univariate and multivariate analyses.Results: High expression of MMP-2, MMP-9, and MT1 -MMP in tumor epithelium was detected in 54%, 97%, and 100% of cases, and in stromal compartments, in 38%, 70%, and 38% of cases, respectively. High stromal expression of MMP-2, MMP-9, and MT1-MMP was significantly associated with aggressive features such as high stage, high grade ascites, and positive lymph node status. Kaplan-Meier analysis showed that high epithelial and stromal expression of MMP-2, MMP-9, and MT1-MMP were each significantly associated with shorter disease-specific survival (DSS; P < 0.01). On tree-structured survival analysis, patients with strong epithelial MT1-MMP expression had the shortest DSS, whereas patients with moderate epithelial MT1-MMP and low stromal MMP-9 expression had the longest DSS (P < 0.01). On multivariate analysis, high stromal expression of MMP-9 (P = 0.01) and MT1-MMP (P = 0.04), strong epithelial MT1-MMP (P = 0.01) and high stage (P = 0.04) were independent predictors of poor DSS.Conclusions: Overexpression of stromal MMP-9 and MT1-MMP is independently associated with shorter DSS in EOC. Thus, host-derived MMPs are valuable predictors of clinical outcome in EOC.