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The Expression And Clinical Significance Of The Matrix Metalloproteinase Inhibitor RECK In Ovarian Epithelial Tumors

Posted on:2009-01-21Degree:MasterType:Thesis
Country:ChinaCandidate:L Y ZhuFull Text:PDF
GTID:2144360242980472Subject:Clinical Medicine
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Background: Ovarian cancer is a common gynecological tumors, all ages have the incidence, but the histological tumor types will vary. Ovarian cancer is female genital mutilation common malignant tumor of the three. Over the past 20 years, due to the application of effective chemotherapy, the malignant ovarian germ cell tumor effect has been significantly improved, the mortality rate downregulated from 90 percent to 10 percent, but the treatment of malignant ovarian epithelial tumors has not been improved, 5 year survival rate hovering at 30%-40%,the first mortality rate was gynecologic malignancies.Epithelial ovarian malignant tumor has become a serious threat of the main tumor to women's lives and health. MMP is the endopeptidase collectively which can degradate the physical circumstances of extracellular matrixion of the basement membrane, and is the most closely related to tumor invasion and metastasis in the class of proteolytic enzymes, MMP-2 and MMP-9 mainly belong to gelatinase, function withⅣcollagen as substrate for type role, and often as non-activity forms exist, and in malignant tumors was increased expression and activation.RECK (reversion inducing cysteine rich proteinwith Kazal motifs) is a newly identified tumor suppressor gene, it has a unique function that inhibit matrix metalloproteinase (matrix matalloproteinases, MMPs) expression and activity, is a kind of matrix metalloproteinase inhibitor. And the expression of RECK gene has closely relation with tumor invasion and metastasis, and angiogenesis, research shows that, RECK gene expression in liver, pancreatic cancer, breast cancer, lung cancer was negatively correlated with tumor invasion, and gene expression higher RECK Patients often are clearly better prognosis in patients with low expression levels.Objective: This paper mainly discusses RECK, MMP-2, MMP-9 and MVD in epithelial ovarian tumors and their clinical significance.Methods: Using immunohistochemical SP detected 13 cases of well-differentiated epithelial ovarian tumors, 23 cases -poorly differentiated epithelial ovarian tumors, 34 patients with ovarian benign organizations and 15 cases of normal epithelial ovarian tissue RECK, MMP-2,MMP-9 expression at the same time observe the different organizations of the microvascular density (MVD).Results: (1) RECK protein expression are mainly located in the cell cytoplasm,yellow or deep yellow, RECK protein in normal and benign ovarian epithelial ovarian tumors has a large number of positive cells,the rates were 80.0%, 88.2%, and the different expression of RECK protein in both was not significant (P=0.3805), and RECK protein in ovarian cancer was significantly reduced, the positive rate was 36.1%, compare with normal ovary and a benign ovarian tumor the difference was significant (χ~2=14.1674, P=0.0008,χ~2=31.8681, P=0). RECK protein in well-differentiated and-poorly differentiated malignant epithelial ovarian tumor expression were 38.5%, 34.8%, there was no significant difference between them (χ~2=0.1851, P=0.9116).RECK protein expressed in the Phase I-II, Phase III-IV malignant epithelial ovarian tumors rates were 57.1%, 22.7%, the expression between the two has no significant difference (χ~2=4.5247, P=0.1041).RECK protein expression in epithelial ovarian cancer patients was unrelated to age (p>0.05).RECK protein expression in epithelial ovarian tumors was unrelated to the pathological type(p>0.05). (2)MMP-2 protein positive staining localization in cells was at the cytoplasm, in brown or yellow or deep yellow. The expression in the normal tissue and ovarian benign epithelial ovarian tumor was low, the expression rates were 33.3%, 23.5%,and the difference was not significant (P=0.7184), MMP-2 protein in malignant ovarian epithelial tumors has high Expression of 69.4%, compare with ovarian normal tissue and benign epithelial ovarian tumors ,there were significant differences (χ~2=6.1085, P=0.0455,χ~2=16.3100, P=0.0003).In ovarian cancer different grade of MMP-2 protein in-poorly differentiated malignant epithelial ovarian tumor is high differentiation of malignant epithelial ovarian tumor expression rate increase, respectively, 46.2%, 82.60%, the difference is significant (P=0.0366).In ovarian cancer the expression of MMP-2 protein in Phase I-II was higher than Phase III-IV in the different clinical stages, their rates were 42.9%, 86.4%, the difference was significant (P=0.0111). the expression of MMP-2 protein in epithelial ovarian cancer patients was unrelated to age (P>0.05). the expression of MMP-2 protein in epithelial ovarian cancer patients was unrelated to pathological type (P>0.05).(3)MMP-9 protein positive staining localization in cells was at the cytoplasm, in brown or yellow or deep yellow.The expression in the normal tissue and ovarian benign epithelial ovarian tumor was low ,the positive rates were 26.7%, 23.5%, the difference between them was not significant (P=0.9727),the expression of MMP-9 in malignant ovarian epithelial tumors was high the expression rates was 69.4%, Compared with ovarian normal tissue and benign epithelial ovarian tumors the differences were significant(χ~2=8.1931, P= 0.0166,χ~2= 15.46734 P=0.0004). The expression of MMP-9 protein in ovarian cancer different levels classification were inceased, 46.2%, 78.3%,the difference was significant(P=0.0478). In the different clinical stages of MMP-9 expression in ovarian cancer in Phase I-II, III-IV respectively rate were 42.9%, 81.8%, the difference between the two was significant (P=0.0183).MMP-9 expression in epithelial ovarian cancer patients was unrelated to age (P>0.05). MMP-9 expression in epithelial ovarian cancer patients was unrelated to pathological type (P>0.05) (4) The the department of microvascular intensive was in mesenchymal and epithelial ovarian junction.The microvessel density in the normal tissue and ovarian benign epithelial ovarian tumor were lower, respectively 12.0933±4.3146, 12.4058±3.5680, the two had no significant difference (P=0.7922), in malignant ovarian epithelial tumors with high expression 24.75±4.8093, and compared with ovarian normal tissue and benign epithelial ovarian tumors the difference were significant (t=8.8127, P=0, t=12.1386, P=0). In ovarian cancer of different levels classification the MVD expressed increased, respectively 20.3692±2.2888,27.2260±4.0237, the difference between the two was significant (P<0.05).In ovarian cancer in the different clinical stages the MVD expression in the Phase I-II, III-IV, were respectively 22.4714±4.3142,26.2±4.6221, the difference between the two was significant (P=0.0210).The expression of MVD in epithelial ovarian cancer patients was unrelated to age (P>0.05). The expression of MVD in epithelial ovarian cancer patients was unrelated to pathological type (P>0.05).(5) the expression of RECK, MMP-2, MMP-9 and MVD.The expression of RECK protein and MMP-2 was significantly negatively correlated (r =-0.5057). The expression of RECK protein and MMP-9 were significantly negatively correlated (r=-0.5725). The expression of MMP-2 and MMP-9 were significantly positive correlation. The expression of RECK positive rate and MVD was significantly negatively correlated (r =-0.383,P=0.021),The expression of MMP-2 positive rate and MVD was significantly positive correlation (r=0.454, P=0.005), The expression of MMP-9 positive rate and MVD was significantly positive correlation (r=0.449, P=0.006).Conclusions: 1. In malignant epithelial ovarian tumor tissues RECK protein expression significantly decreased, suggesting that the expression of RECK gene in the tumor tissue was reduced, so that the invasion of ovarian cancer cells was increased. 2. The expression of MMP-2, MMP-9 protein in malignant epithelial ovarian tumor has a significant increase ,the expression was significantly increased with the texture histologic grade, clinical period. In the course of malignant epithelial ovarian tumor invasion and metastasis the two has played an important role. 3. Microvascular density (MVD) in malignant epithelial ovarian tumors was significantly increased. The expression of microvessel density (MVD) was significantly increased with the texture histologic grade, clinical stage. Note that certain factors in malignant epithelial ovarian tumors led to the microvascular density (MVD) increased, but the increase in microvascular density lead to the malignant tumor invasion and metastasis. 4.In malignant epithelial ovarian tumor tissues RECK protein expression significantly decreased, and the expression of MMP-2 protein, MMP-9 protein and microvascular density (MVD) was markedly increased. With the texture histologic grade, clinical stage ,The first three joint can be detected as a prediction of common epithelial ovarian tumors of the degree of malignancy and metastasis of important indicators. 5. With the improvement of clinical stages, RECK protein expression was significantly reduced, suggesting that RECK missing state epithelial ovarian tumor cell invasion was markedly improved, and likely to be ovarian cancer invasion and metastasis, and RECK, MMP-2 protein, MMP-9 protein and microvascular density (MVD) in a negative correlation between the expression of RECK.Research and treatment methods for new anticancer drug development provides a new way of thinking, for human epithelial ovarian tumors treatment provides a new target.
Keywords/Search Tags:RECK, matrix metalloproteinase-2, matrix metalloproteinase-9, microvascular density, epithelial ovarian tumors
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