Department of Obstetrics, Hôpital Tenon, AP-HP, F-75571 Paris, France.
Oncol Rep. 2012 Apr;27(4):1049-57. doi: 10.3892/or.2011.1608. Epub 2011 Dec 22.
Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in tumor invasion, but their prognostic significance is still under discussion. We set out to analyze the epithelial and stromal expression of MMP-2, MMP-7, MMP-9, MT1-MMP, TIMP-1 and TIMP-2 in advanced epithelial ovarian cancers and to assess their prognostic value. A tissue microarray of malignant ovarian tumors from 69 patients was constructed. Immunostaining results were scored using the HSCORE and assessed by univariate analysis with Bonferroni correction and classical multidimensional scaling (CMDS). Kaplan-Meier survival curves calculated with regard to patient and tumor characteristics were compared by the log-rank test. Patients treated by primary surgery (n=43) had a higher tumor size and a trend toward higher epithelial MMP and TIMP expression than those treated by interval surgery (n=26). Optimal cytoreduction (residue ≤ 1 cm) was obtained in 27 and 18 patients, respectively. Clinical and histological characteristics were not different in patients with optimal cytoreduction and those with suboptimal cytoreduction. The expression of epithelial MMP-9 (P=0.002) and TIMP-2 (P=0.026) were higher in the latter group. CMDS failed to demonstrate any influence of MMP and TIMP expression with regard to cytoreduction outcome. MMP and TIMP expression did not influence survival. Their prognostic values were outweighed by histological type, lymph node involvement and cytoreduction. Standard statistical analysis adjusted after Bonferroni correction and CMDS reduced the relevance of MMPs and TIMPs in the prognosis of patients with advanced ovarian cancer.
基质金属蛋白酶（MMPs）及其组织抑制剂（TIMPs）参与肿瘤侵袭，但它们的预后意义仍在讨论中。我们旨在分析晚期上皮性卵巢癌中 MMP-2、MMP-7、MMP-9、MT1-MMP、TIMP-1 和 TIMP-2 的上皮和基质表达，并评估其预后价值。构建了 69 例恶性卵巢肿瘤的组织微阵列。使用 HSCORE 对免疫染色结果进行评分，并通过单因素分析（Bonferroni 校正）和经典多维尺度分析（CMDS）进行评估。根据患者和肿瘤特征计算 Kaplan-Meier 生存曲线，并通过对数秩检验进行比较。接受初次手术治疗的患者（n=43）肿瘤较大，上皮 MMP 和 TIMP 表达呈上升趋势，而接受间隔手术治疗的患者（n=26）则无此趋势。分别有 27 例和 18 例患者获得最佳肿瘤细胞减灭术（残余≤1cm）。最佳肿瘤细胞减灭术患者与非最佳肿瘤细胞减灭术患者的临床和组织学特征无差异。后者上皮 MMP-9（P=0.002）和 TIMP-2（P=0.026）的表达更高。CMDS 未能证明 MMP 和 TIMP 表达与肿瘤细胞减灭术结果之间存在任何影响。MMP 和 TIMP 的表达并不影响生存。它们的预后价值被组织学类型、淋巴结受累和肿瘤细胞减灭术所超越。Bonferroni 校正和 CMDS 后进行的标准统计学分析降低了 MMPs 和 TIMPs 在晚期卵巢癌患者预后中的相关性。
