Expression of MMP-2, −7, −9, MT1-MMP and TIMP-1 and −2 has no prognostic relevance in patients with advanced epithelial ovarian cancer

Abstract

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.

Resveratrol inhibits IL‐6‐induced ovarian cancer cell migration through epigenetic up‐regulation of autophagy

“…d-Catenin promotes malignant phenotypes by non-competitive binding to E-cadherin [61] MMP7 (metalloprotease) Matrix metalloproteinases (MMPs) are involved in tumor invasion [62] PLAT (plasminogen activator) The urokinase plasminogen activator plays an important role in tumor invasion and metastasis in ovarian cancer [63] FGFBP1 (fibroblast growth factor binding protein 1)…”

Ovarian cancer: involvement of the matrix metalloproteinases

“…Hence, the overview presented herein highlights some of these findings emphasizing the similarities and controversies. Brun and coworkers have extensively characterized the localization and expression levels of MMP 2, 7, 9 and MT1 in different types and stages of ovarian cancer (Brun et al 2008, Brun et al 2012). They report that serous tumors express higher levels of MMP2, 7, and 9 compared to mucinous tumors.…”

“…In fact, MMP2 is more frequently expressed in benign tumors than in carcinomas (Brun et al 2012). These discrepancies may be due to the different methods that the investigators have used to analyze the samples as well as the arbitrary thresholds that were put in place by the different groups to determine staining intensity upon immunohistochemistry analysis (Brun et al 2012). …”

Pancreatic adenocarcinoma up‐regulated factor has oncogenic functions in oral squamous cell carcinoma

“…Statistical analysis was performed using Fisher's exact, χ 2 and Student's t ‐tests. Because of multiple comparisons in immunohistochemistry, Bonferroni correction of alpha significance level was performed . P ‐values less than alpha significance level were regarded as statistically significant.…”