| Background and Objective:Cervical carcinoma is the second big rates of malignant tumors in women, in recent years, with the wide application of the cervical fall off cytologic examination, the detection rate of cervical cancer increases greatly.Cervical squamous cell carcinoma is the most common pathological type in cervical cancer,high invision and transfer are its characteristics, although the application of many kinds of comprehensive treatment measures including traditional surgery, radiotherapy, chemotherapy and so on, have significantly improved the patient’s quality of life, the invasion and metastasis in cervical cancer are still the main causes of many treatment failures and deaths. At present, the diagnosis of cervical cancer is not difficult, recognizing the biological behavior of the cells of cervical squamous cell carcinoma, discussing the mechanism of its invasion and metastasis, looking for a specific gene target which could inhibit its invasion and metastasis, developping new biological engineering antitumor drugs, are currently the key problems waiting to solve.The occurrence of cancer development, invasion and metastasis is a long-term and complex process which involved in more stages, more steps, many factors, the activation of oncogenes, tumor-suppressor genes inactivation and over-expression or missing of a variety of protein factors caused by the former. Annexin A2is a Ca2+-mediated phospholipid binding protein which involved in the formation of the membrane skeleton, membrane aggregation, endocytosis,exocytosis and a series of physiological activities which depends on Ca2+. Studies have found that on the surface of tumor cell, Annexin A2could combine with tissue fibrinolytic enzyme original activation agent (t-pa), fibrinolytic enzyme original (PLG), fibrinolytic enzyme, cell integrin C, tissue protease B, S100A4, tendon glycoprotein-C (TN-C), and make many kinds of factors regionalized, then it could stimulate the enzyme reactions and promote the degradation of extracellular matrix and accelerate the tumor cells infiltrating into the surrounding tissue, lymph nodes and distant metastases. CD147, extracellular matrix metalloproteinases induced factor, is a kind of single type I glycoprotein across a cell membrane,widely expressed on the cell membrane surface, belonging to the immunoglobulin superfamily (IgSF) members, CD147could induce tumor cells and surrounding fibroblasts to secrete MMPs, including:MMP-1, MMP-2, MMP-3, MMP-9, MMP-11etc, and the latter almost could degrade all the ingredients of extracellular matrix, in recent years, a large number of studies have found that CD147were highly expressed in a wide variety of tumor cells. MMP-2, also known as gelatinases A, is an important member of the family of MMPs, could degrade gelatin, IV, V, Ⅶ, X collagen, FN and elastic fiber and so on many kinds of components, the activated MMPs concentrated in the prominent parts where cells penetrate through matrix, which played a major role in digesting cell matrix and the main components of the basement membrane.Articles about combining test of Annexin A2, CD147, MMP-2in the tissue of cervical squamous cell carcinoma, and the relationship between these three proteins above and tumorigenesis and tumor progression,have not been reported in the literature. This experiment used immunohistochemical SP method to detect the expressions of Annexin A2, CD147, MMP-2in14cases of cervical normal squamous epithelial tissues,31cases of cervical intraepithelial neoplasia (CIN) tissues and39cases cervical squamous cell carcinoma tissues.lt also aims to analysis the connections between the expressions of these three proteins and the clinical datas of cervical squamous cell carcinoma, discuss the relationships of these three and possible existing mechanisms, find some protein factors that would be able to evaluate the clinical characteristics and the malignant degree of cervical cancer, and so as to explore new ways of gene therapy of cerical cancer.Methods:1. The experiment used immunohistochemical SP method to detect the expressions of Annexin A2, CD147, MMP-2in14cases of normal cervical squamous epithelial tissues,31cases of cervical intraepithelial neoplasia tissues (CIN) and39cases of cervical squamous cell carcinoma tissues, respectively.2. Statistical analysis:All datas were analyzed by SPSS17.0statistical software package, we used the chi-square test (chi-square) for the positive comparsion, Wilcoxon rank sum test of two independent samples or Kruskal Wallis H rank sum test of two more groups and ordinal classification materials was used for the comparsion of the strength of the expressions. We used the correlation analysis of2x2or3x2contingency table for positive correlation analysis, and Spearmen rank correlation analysis for the strength of the expressions.The level of significant difference was a=0.05.Results:1. The positive expression rates of Annexin A2protein in cervical normal squam ous epithelial tissue, cervical intraepithelial neoplasia tissue (CIN) and cervical squamous cell carcinoma tissue were35.71%(5/14),61.29%(19/31),89.74%(35/39), respectively. The positive expression rates of Annexin A2and its expression strength in cervical normal squamous epithelial tissue, CIN tissue were significantly lower than that in cervical squamous cell carcinoma tissue with statistically difference (P<0.05); comparisons between any two groups, the positive expression rates of Annexin A2and its expression strength in cervical normal squamous epithelial tissue and CIN tissue had no statistically difference(P>0.017);but in groups of cervix normal squamous epithelial tissue-cervical squamous cell carcinoma tissue and CIN tissue-cervical squamous cell carcinoma tissue,the positive expression rates and expression strength of Annexin A2were both statistically significant (P<0.017). No statistically difference had shown in all three degrees of CIN tissues both in positive expression rates and expression strength of Annexin A2(P>0.05). The positive expression rates and expression strength of Annexin A2had no correlation with squamous metaplasia of the glandular epithelium and involvement of the glands; the positive expression rate of Annexin A2protein in tissues with squamous metaplasia of the glandular epithelium was52.38%(11/21),while it was55.56%(5/9) in tissues without squamous metaplasia of the glandular epithelium,and positive expression rates and expression strength were both not significantly different (P=1.000); the positive expression rate of Annexin A2protein in tissues with involvement of the glands was53.85%(7/13),while it was50.00%(1/2) in tissues without involvement of the glands,both the positive expression rates and expression strength were not significantly different (P=1.000). The expressions of Annexin A2protein were irrelevant with cervical cancer patients’age, tumor differentiation grade, and lymph node metastasis; the positive expression rate of Annexin A2was88.24%(15/17) in the tissue of age less than45, it was90.91%(20/22) in the tissue of age more than equal to45, the positive expression rates and expression strength of Annexin A2in two groups were both not statistically significant (P>0.05). According to the classification sorted by the tumor differentiation degree,the positive expression rates of Annexin A2in Degree I, Degree Ⅱ, DegreeⅢ were86.67%(13/15),87.50%(14/16),100%(8/8), respectively, the positive expression rates and expression strength of Annexin A2in three degrees showed no statistically difference(P=0.561). The positive expression rate of Annexin A2in tissues with lymph node metastasis was75.00%(12/16),and it was91.30%(21/23) in tissues without lymph node metastasis, the positive expression rates and expression strength of Annexin A2in two groups were not statistically significant (P>0.05). The positive expression rates of Annexin A2protein and tumor infiltration depth were positively related (r expression positive ratc=0.376, P=0.011). In23cases of tissues with tumor infiltration percentage more than equal to67%,the positive expression rate of Annexin A2protein was100%(23/23), while in16cases of tissues with tumor infiltration percentage less than67%,the positive expression rate of Annexin A2protein was75.00%(12/16); difference of the two groups was statistically significant in positive expression rate(rexpression positive rate=0.376, P=0.011), but not in expression strength(P>0.05).2. The positive expression rates of CD147protein in cervical normal squamous epithelial tissue, cervical intraepithelial neoplasia tissue (CIN) and cervical squamous cell carcinoma tissue were35.71%(5/14),67.74%(21/31),89.74%(35/39),respectively. The positive expression rates of CD147and its expression strength in cervical normal squamous epithelial tissue, CIN tissue were significantly lower than that in cervical squamous cell carcinoma tissue with statistically difference (P<0.05); comparisons between any two groups, the positive expression rates of CD147and its expression strength in cervical normal squamous epithelial tissue and CIN tissue had no statistically difference(P>0.017); the difference of positive expression rates of CD147in CIN tissues and cervical squamous cell carcinoma tissues were not statistically significant,but its expression strength in two groups were statistically significant (P<0.017);the positive expression rates and expression strength of CD147were both statistically significant between the tissues of cervical normal squamous epithelial and cervical squamous cell carcinoma (P<0.017). No statistically difference had shown in all three degrees of CIN tissues both in positive expression rates and expression strength of CD147(P>0.05). The positive expression rates and expression strength of CD147had no correlation with squamous metaplasia of the glandular epithelium and involvement of the glands; the positive expression rate of CD147protein in tissues with squamous metaplasia of the glandular epithelium was42.86%(9/21),while it was55.56%(5/9) in tissues without squamous metaplasia of the glandular epithelium,and positive expression rates and expression strength were both not significantly different (P=0.694); the positive expression rate of CD147protein in tissues with involvement of the glands was76.92%(10/13),while it was100%(2/2) in tissues without involvement of the glands,both the positive expression rates and expression strength were not significantly different (P=1.000). The expressions of CD147protein were irrelevant with cervical cancer patients’age, tumor differentiation grade, and lymph node metastasis; the positive expression rate of CD147was88.24%(15/17) in the tissues of age less than45, it was90.91%(20/22) in the tissue of age more than equal to45, the positive expression rates and expression strength of CD147in two groups were both not statistically significant (P>0.05). According to the classification sorted by the tumor differentiation degree,the positive expression rates of CD147in Degree I, Degree II, DegreeⅢ were86.67%(13/15),87.50%(14/16),100%(8/8), respectively, the positive expression rates and expression strength of CD147in three degrees showed no statistically difference(P=0.561). The positive expression rate of CD147in tissues with lymph node metastasis was93.75%(15/16),and it was86.96%(20/23) in tissues without lymph node metastasis, the positive expression rates and expression strength of CD147in two groups were not statistically significant (P>0.05). The positive expression rates and expression strength of CD147protein were positively related with tumor infiltration depth (rexpression positive rate=0.376, P=0.011; r expression strength=0.421, P=0.008). In23cases of tissues with tumor infiltration percentage more than equal to67%, the positive expression rate of CD147protein was100%(23/23), while in16cases of tissues with tumor infiltration percentage less than67%, the positive expression rate of CD147protein was75.00%(12/16); difference of the two groups was statistically significant both in the positive expression rates and expression strength (P<0.05).3. The positive expression rates of MMP-2protein in cervical normal squamous epithelial tissue, cervical intraepithelial neoplasia tissue (CIN) and cervical squamous cell carcinoma tissue were14.29%(2/14),51.61%(16/31),82.05%(32/39),respectively. The positive expression rates of MMP-2and its expression strength in cervical normal squamous epithelial tissue, CIN tissue were significantly lower than that in cervical squamous cell carcinoma tissue with statistically difference (P<0.05); comparisons between any two groops, the positive expression rates of MMP-2and its expression strength in cervical normal squamous epithelial tissue and CIN tissue had no statistically difference(P>0.017); but in groups of cervix normal squamous epithelial tissue-cervical squamous cell carcinoma tissue and CIN tissue-cervical squamous cell carcinoma tissue,the positive expression rates and expression strength of MMP-2were both statistically significant (P<0.017). No statistically difference had shown in all three degrees of CIN tissues both in positive expression rates and expression strength of MMP-2(P>0.05). The positive expression rates and expression strength of MMP-2had no correlation with squamous metaplasia of the glandular epithelium and involvement of the glands; the positive expression rate of MMP-2protein in tissues with squamous metaplasia of the glandular epithelium was33.33%(7/21),while it was22.22%(2/9) in tissues without squamous metaplasia of the glandular epithelium,and positive expression rates and expression strength were both not significantly different (P=0.681);the positive expression rate of MMP-2protein in tissues with involvement of the glands was61.54%(8/13),while it was50.00%(1/2) in tissues without involvement of the glands,both the positive expression rates and expression strength were not significantly different (P=1.000). The expressions of MMP-2protein were irrelevant with cervical cancer patients’age, tumor differentiation grade, the tumor infiltration depth and lymph node metastasis, but the expression strength was involved with tumor infiltration depth and lymph node metastasis. The positive expression rate of MMP-2was88.24%(15/17) in the tissues of age less than45,it was77.27%(17/22) in the tissues of age more than equal to45, the positive expression rates and expression strength of MMP-2in two groups were both not statistically significant (P>0.05). According to the classification sorted by the tumor differentiation degree,the positive expression rates of MMP-2in Degree I, Degree II, DegreeⅢ were66.67%(10/15),87.50%(14/16),100%(8/8), respectively, the positive expression rates and expression strength of MMP-2in three degrees showed no statistically difference(P=0.106). The positive expression rate of MMP-2in tissues with lymph node metastasis was87.50%(14/16), and it was78.26%(18/23) in tissues without lymph node metastasis, the positive expression rates of MMP-2in two groups were not statistically significant (P>0.05). In23cases of tissues with tumor infiltration percentage more than equal to67%, the positive expression rate of MMP-2protein was91.30%(21/23), while in16cases of tissues with tumor infiltration percentage less than67%, the positive expression rate of MMP-2protein was68.75%(11/16); the positive expression rates of MMP-2protein and tumor infiltration depth were not positively related(P>0.05). But MMP-2expression strength and tumor infiltration depth, lymph node metastasis were positively related (r,umOr infiltration dePth=0.319,P=0.048; r lymph nodc mctastaSis=0.327,P=0.042).4. The co-expression of Annexin A2, CD147and MMP-2had nothing to do with squamous metaplasia of the glandular epithelium and involvement of the glands. The positive co-expression rate of Annexin A2, CD147, MMP-2was79.49%(31/39) in cervical squamous cell carcinoma tissues, the co-expression of these three proteins had nothing to do with cervical carcinoma patient’s age, tumor differentiation grade, and lymph node metastasis, but tumor infiltration depth. The positive co-expression rate of these three proteins was82.35%(14/17) in the tissues of age less lhan45,it was77.27%(17/22) in the tissues of age more than equal to45, the positive expression rates in two groups were both not statistically significant (P>0.05). According to the classification sorted by the tumor differentiation degree,the positive co-expression rates of Annexin A2,CD147,MMP-2in Degree I, Degree II, DegreeⅢ were66.67%(10/15),81.25%(13/16),100%(8/8), respectively, the positive co-expression rates in these three degrees showed no statistically difference(P>0.05). The positive co-expression rate of Annexin A2,CD147,MMP-2in tissues with lymph node metastasis was87.50%(14/16),and it was73.91%(17/23) in tissues without lymph node metastasis, the positive co-expression rates of these three proteins in two groups were not statistically significant(P>0.05). In23cases of tissues with tumor infiltration percentage more than equal to67%,the positive co-expression rate of these three proteins was91.30%(21/23), while in16cases of tissues with tumor infiltration percentage less than67%,the positive co-expression rate of these three proteins was62.50%(10/16),the difference of the positive co-expression rate of these three proteins was statistically significant (P<0.05),the co-expression of Annexin A2,CD147,MMP-2was positively related with tumor invasion depth(r=0.331,P=0.028).5. The expressions of Annexin A2and CD147were positively related (r=0.405, P=0.006), the expression of Annexin A2and MMP-2were positively related (r=0.586, P=0.000), the expressions of CD147and MMP-2also had a positive correlation (r=0.488, P=0.000), in cervical squamous cell carcinoma tissues.Conclusion:1. Annexin A2, CD147and MMP-2may be involved in the process of incidence of cervical squamous cell carcinoma.2. The overexpression of Annexin A2, CD147and MMP-2proteins were relevant with the infiltration of cervical squamous cell carcinoma, MMP-2may also be involved in the process of lymph node metastasis of cervical squamous cell carcinoma.3. Annexin A2, CD147and MMP-2had positive relation between any two of them in cervical squamous cell carcinoma tissues, and co-expression of these proteins was closely related with the depth of tumor invasion, it suggested that these three proteins may be synergetic among them in the prosess of infiltration in cervical squamous cell carcinoma. |
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