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Research On The Relationship Between The Expression Of Cathepsin B, MMP-9 And Infiltration, Metastasis In Squamous Carcinoma Of The Cervix

Posted on:2008-07-16Degree:MasterType:Thesis
Country:ChinaCandidate:J L ZhouFull Text:PDF
GTID:2144360215960293Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
Cathepsin B is a kind of cysteine proteinase of Cytolysosome, Participating in physiological process such as protein degradation, bone remodeling and antigen presentation and so on. The research indicated that the abnormal expression and location of CB may lead to pathological reaction, The expression and activity of CB in many sorts of tumor tissues are obviously higher than those in adjacent normal tissues. The reinforcement of expression and activity of CB in tumor cells contribute to degrading main component of extracellular matrix-Laminin and type IV collagen and invasion and diffusion, Moreover activating urokinase-type plasminogen activator, matrix metalloproteinase that can degrade extracellular matrix and so on. matrix metallproteinases,MMPs is proteinase of Zn dependence, which is a sort of endopeptidase that can degrade extracellular matrix and basement membrane. Among them MMP-9 is a kind of metalloproteinase and is named after type IV collagenase or gelatinase B and enzyme of the biggest molecular weight of MMPs family. Available research demonstrated that MMP-9 could degrade extracellular matrix, participating in neovascularization of tumor and regulating cell adhesion and so on, thus playing the important roles during the process of infiltration and metastasis of rumor cells. The research showed that MMP-9 presented overexpression and was closely relative to infiltration,metastasis of tumor in many kinds of malignant tumors such as gastric cancer, cancer of the breast, thyroid carcinoma and lung cancer and so on.Cancer of the cervix is one of the most frequent female malignant tumors and possesses higher disease incidence and tends to young and possesses higher metastasis and recurrence rate and poor prognosis. Infiltration and metastasis is one of main causes of death of patients with cervical cancer of advanced stage. Occurrence, development and infiltration, metastasis of cancer of the cervix are a series of processes of multiple factor, multiple stage, polygene, which participated in, therefore, to find the indexes that is relative to infiltration and metastasis of tumor has become one of hot spots of research. Concerned with research of the expression of CB and MMP-9 in squamous carcinoma of the cervix and its relationship with infiltration and metastasis of tumor, there are not document reports in domestic and external country to this day, furtherly discussing the expression of CB and MMP-9 protein and its relationship with infiltration and metastasis of cancer of the cervix, searching detecting the indexes of occurrence, development and infiltration, metastasis of cancer of the cervix and effective methods of suppressing infiltration, metastasis of cancer of the cervix, Our research adopts immunohistochemistry method, observing the expression of CB, MMP-9 protein in cervical squamous carcinoma tissues of 45 cases, cervical intraepithelial neoplasia tissues of 63 cases and normal cervical epithelium tissues of 33 cases respectively and explores their relationship from each other and mechanism of action, Our research furtherly illuminated mechanism of infiltration and metastasis of uterine cervix carcinoma and provided rationale for clinical therapy of cancer of the cervix.Materials and Methods1. The operating samples came from the Third Affiliated Hospital of Zhengzhou University from May 2004 to October 2006, including 45 cases of squamous cell carcinoma of uterine cervix, and 63 cases of cervical intraepithelial neoplasia and 33 cases of normal cervical epithelium tissues.2. Using the technology of immunohistochemistry SP to detect the expression of CB, MMP-9 protein in the 45 cases of squamous cell carcinoma of uterine cervix, and 63 cases of cervical intraepithelial neoplasia tissues and 33 cases of normal cervical epithelium tissues respectively .In addition, several clinic pathological feature was analyzed.3. Statistical analysis: All the data was analyzed by SPSS 10.0 statistical package, the count information calculated the positive rate. The comparison of positive rate uses the Chi-square ; the relation of two variable was analyzed by the spearman level correlation analysis.The level of significant difference isα=0.05.Results1. Immunohistochemical results indicated: the positive expression rate of CB protein in normal cervical epithelium tissues was 0% (0/33) ; The positive expression rate of CB protein in cervical intraepithelial neoplasia tissues was 30.15% (19/63) ; The positive expression rate of CB protein in the cervical carcinoma tissues was 55.56% (25/45), the positive expression rate of CB protein in the carcinoma tissues was compared with that in the cervical intraepithelial neoplasia tissues and normal cervical epithelium tissues from each other, there was statistical significance( P <0.01).The positive expression of CB protein raised was followed by differentiated extent of squamous carcinoma of the cervix, there was statistical significance( P <0.05).2.Immunohistochemical results indicated: the positive expression rate of MMP-9 protein in normal cervical epithelium tissues was 6% (2/33 ) ; The positive expression rate of MMP-9 protein in cervical intraepithelial neoplasia tissues was 41.27% (26/63 ); the positive expression rate of MMP-9 protein in the carcinoma tissues was 71.11% (32/45), the positive expression rate of MMP-9 protein in the carcinoma tissues was compared with that in the cervical intraepithelial neoplasia tissues and normal cervical epithelium tissues from each other, there was statistical significance( P<0.01).The positive expression of MMP-9 protein raised was followed by differentiated extent of squamous carcinoma of the cervix, there was statistical significance( P <0.05).3.With the increasing of infiltrating depth, the positive expression rate of CB and MMP-9 protein was increasing obviously. In the tissues of cancer of the cervix, the positive expression rate of CB protein in the one second cervix invaded, over one second cervix invaded was 33.33%(6/18), 70.37%(19/27) respectively, there was statistical significance between two groups (P < 0.05) ; the positive expression rate of MMP-9 protein in the one second cervix invaded, over one second cervix invaded was 50.00%( 9/18), 85.18%(23/27) respectively, there was statistical significance between two groups (P<0.05) .4. With lymphatic metastasis of carcinoma cells, the positive expression rate of CB and MMP-9 protein was increasing obviously, in the tissues of carcinoma, the positive expression rate of CB protein with lymphatic and non-lymphatic metastasis was 90%(18/20), 28%(7/25) respectively, there was statistical significance between two groups (P<0.01); the positive expression rate of MMP-9 protein with lymphatic and non-lymphatic metastasis was 95.00%(19/20), 52%(13/25)respectively, there was statistical significance between two groups (P<0.01).5.The relativity of the expression of CB and MMP-9 was analyzed by statistics, results showed that there is a positive correlation between both(P<0.01).Conclusions1. The positive expression rate of CB protein is higher in the tissues of squamous carcinoma of the cervix, heightening with differentiated extent decreasing and with lymphatic metastasis and increasing of infiltrating depth, it indicated that CB participated in occurrence, development, infiltration and metastasis of squamous carcinoma of the cervix.2. The positive expression rate of MMP-9 protein increases gradually from normal cervical epithelium, cervical intraepithelial neoplasia to the tissues of carcinoma, heightening with differentiated extent decreasing and with lymphatic metastasis and increasing of infiltrating depth, it indicated that MMP-9 participated in occurrence, development, infiltration and metastasis of squamous carcinoma of the cervix.3. The relationship of expression of CB and MMP-9 protein in squamous carcinoma of the cervix was positive correlation between them. Results showed that they played synergistic effect during the process of occurrence, development, infiltration and metastasis of squamous carcinoma of uterine cervix.
Keywords/Search Tags:squamous carcinoma of the cervix, CB, MMP-9, infiltration, metastasis
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