Research On Expression And Correlation Of Ang-2 And VEGF In Cervical Carcinoma Tissues

Objective:Cervical carcinoma is the most common malignant tumor in the femilar reproductive system in our country, and about 80,000 die of the disease annually. Cervical intraepithelial neoplasia is a precarcinomaous lesion of cervical carcinoma from CIN to CC about the development experience of 5-10 years. Although cervical carcinoma and cervical intraepithelial neoplasia is the result of a multi-factor of common occurrence, the occurrence and development of tumor angiogenesis must provide nutrition and material supply, so angiogenesis in carcinoma growth and metastasis of infiltrating plays an important role. Angiogenesis is a primitive vascular plexus or it has been in existence such as blood vessels formed by sprouting angiogenesis process, involving multi-cellular regulation. Ang is the only receptor containing receptor agonists and inhibitors of angiogenesis regulatory factors (of which the most representative is Ang2 with much research value). VEGF is the most important vascular growth factor ever found up to date, in a variety of tumor tissues high expression, and it has promoted the proliferation and metastasis of tumors. At present, VEGF in cervical carcinoma tissues and its relationship with malignant tumor growth and metastasis of the research have attracted wide attention from scholars. However, there have been less reports on Ang2 and cervical carcinoma angiogenesis and VEGF expression of Ang2 and the relevance of studies. This paper, by detecting Ang2 and VEGF in the normal cervix, CIN and cervical carcinoma tissues, studies the correlation between the two to explore the important role in the occurrence of angiogenesis in carcinoma, development and transfer so as to provide theoretical and experimental basis for anti-angiogenic carcinoma therapy.Methods:This experiment adopts the immunohistochemical SP method, the application of Ang2 polyclonal antibody (working concentration was 1:50)and VEGF monoclonal antibodies(working concentration was 1:100),which was bought from Beijing Biosynthesis Biotechnology Corporation and Maixin Biotechnology Corporation,respectively,to detect protein levels from Ang2 and VEGF in 20 cases of normal cervical tissue, 32 cases of cervical intraepithelial neoplasia (CINⅠgrade 12 cases, CINⅡ-ⅢGrade 18 cases), and 52 cases of cervical carcinoma tissues. Cervical carcinoma is divided into phases according to FIGO staging criteria, eight cases ofⅠa period,Ⅰb 10 period,Ⅱa 14 period andⅡb 11 period, and nine cases ofⅢ-Ⅳperiod; according to the WHO classification of histological types: 33 cases of squamous cell carcinoma, 13 cases of adenocarcinoma, and six cases of adenocarcinoma, squamous; according to pathological degree of differentiation: 18 cases of well differentiatioin, 22 cases of medium differentiation, and 12 cases of low differentiation; 15 cases of lymph node metastasis, and 37 cases without lymph node metastasis. All the patients did not receive radiotherapy or chemotherapy, with complete clinical data. The results were classified according to the following stadards:The expression site of Ang2 and VEGF were mainly in the plasma and the positive staining were dark yellow and brown. The score standards of staining level as follows: barely tinction was seen as 0 score, buff was 1 scores , dark yellow was 2 and dark brown was 3(under 10×10 field). The percentage assessment norm of positive staining cells:select five high power field randomly and count the positive cell population per field ,which was 0 score when the percentage of the mascular cell was <5%,6% -25% was 1,26%-50% was 2 and >51% was 3 scores(under 40×10 field).Then plus staining level and The positive percentage of staining cells of each slide:≤2 was negative,>2 was positive,among which 0-1 score was(-),2 scores belong to(+),3-4 scores was(++) and >6分was(+++).SPSS13.0 statistical software for data processing, X2 test and Fisher's exact probability method for comparing samples of positive expression, Spearman rank correlation analysis of Ang2 and VEGF relevance are adopted.Results:1. From normal cervical tissues to CIN to cervical carcinoma group, the Ang2 positive expression rate is increased progressively. Ang2 in cervical carcinoma and positive expression rate is 59.62%, significantly higher than that of cervical intraepithelial neoplasia (18.75%) and normal cervical tissue (10%), showing significant difference(P<0.05); Ang2 in cervical carcinoma and cervical intraepithelial neoplasia tissues is compared, showing very significant difference(P<0.01); Ang2 in cervical intraepithelial neoplasia and normal cervical tissues is compared, showing no significant difference.2. The positive expression level of Ang2 between≤35 and >35 age groups were no quiet difference ( P>0.05 ) and no statistical significance. The Ang2 expression in different pathologicaltypes of cervical carcinoma, such as squamous caicinoma of the cervix, adenocarcinoma and adenosquamous carcinomoa, was no difference and no significance in statistics(P>0.05).In the well, middle and poorly differentiated cervical carcinoma, the expression difference of Ang2 protein was obsolete(P>0.05).FIGO clinical stageⅢ-Ⅳpatients with Ang2 protein expression level is significantly higher than that in stageⅠandⅡpatients, showing a significant difference(P<0.05). The Ang2 protein expression level in patients with lymph node metastasis is significantly higher than that in patients with no lymph node metastasis, showing very significant difference(P<0.01).3. From normal cervical tissues to CIN to cervical carcinoma group, the VEGF positive expression rate is increased progressively. VEGF in cervical carcinoma and positive expression rate is 69.23%, significantly higher than that of cervical intraepithelial neoplasia (21.88%) and normal cervical tissue (10%), showing significant difference(P<0.05); VEGF in cervical carcinoma and cervical intraepithelial neoplasia tissues is compared, showing very significant difference(P<0.01); VEGF in cervical intraepithelial neoplasia and normal cervical tissues is compared, showing statistical significance(P<0.05)4. The positive expression level of VEGF protein between≤35 and >35 age groups were no quiet difference(P>0.05)and no statistical significance. The VEGF expression in different pathologicaltypes of cervical carcinoma, such as squamous caicinoma of the cervix, adenocarcinoma and adenosquamous carcinomoa, was no difference and no significance in statistics(P>0.05).In the well, middle and poorly differentiated cervical carcinoma, the expression difference of VEGF protein was obsolete(P>0.05). FIGO clinical stageⅢ-Ⅳpatients with VEGF protein expression level is significantly higher than that in stageⅠandⅡpatients, showing a significant difference(P<0.05). VEGF protein expression level in patients with lymph node metastasis is significantly higher than that in patients with no lymph node metastasis, showing significant difference(P<0.05).5. In carcinoma tissues, the VEGF protein expression in patients with positive Ang2 protein expression is obviously higher. Spearman rank correlation analysis shows that the two are positively correlated (r = 0.640, P <0.01).Conclusions:1. Ang2 is likely involved in carcinoma angiogenesis, impacting carcinoma occurrence and growth.2. The abnormal expression of Ang2 may play a catalytic role in the invasion and metastasis of cervical carcinoma as a factor determining the prognosis of cervical carcinoma.3. VEGF plays an important role in the process of changes from normal cervical tissue to cervical intraepithelial neoplasia and cervical angiogenesis. It can promote blood vessel generation, occurrence of cervical carcinoma and its growth.4. The abnormal expression of VEGF may play a catalytic role in the invasion and metastasis of cervical carcinoma as a factor determining the prognosis of cervical carcinoma.5. Ang2 and VEGF in carcinoma angiogenesis have interactions and jointly promote the growth and metastasis of cervical carcinoma.