Expression And Clinical Significance Of Annexin A2, Nf-κbp65 And Ki-67 In Cervical Cancer

ackground and Objective:Cervical cancer is one of the most common gynecology malignant tumors, sees in married woman. Its disease incidence rate is only inferior to breast cancer in the global female malignant tumor, occupies more than half of the female reproductive organs tumor, occupies the first place in the developing country. The Chinese cervical cancer morbidity peak age is 45-49 years old, in recent years, cervical cancer's morbidity tended the youth oriented. This threaten seriously feminine life and health, therefore, conducts the deep research is very essential to cervical cancer's occurrence development mechanism.The occurrence of tumor are very complex gene regulatory networks, are multi-gene, multi-stage, multi-factor process, and many are closely related to gene mutation. In recent years, the cell multiplication already became the hot spot in the tumor research. Annexin A2 in DNA synthesis and cell proliferation play an important role, In a variety of malignant tumor tissues it was significantly increased. NF-KBp65 is a many dominant nuclear transcription factor, and is closely related with tumor cell growth, proliferation, invasion and metastasis. Ki-67 is a nuclear cell proliferation-related antigen, is a sensitive indicator of cell proliferation. Examine the expression of Annexin A2, NF-κBp65 and Ki67 in invasive carcinoma of cervix uteri (ICC), cervical intraepithelial neoplasia (CIN) and normal cervical epithelium by immunohistochemistry SP. Explore the expression and the relationship between the occurrence and development of cervical cancer and its possible mechanism.Materials and methods:1. 113 cervical tissues keeping in the archives in the Department of Pathology, the First Affiliated Hospital of ZhengZhou University from January 2005 to January 2007 were included in the study, which consisted of 24 cases of CIN, average age 38.83 years old, 8 cases of CINⅠ, 7 cases of CINⅡ, 9 cases of CINⅢ. 74 cases of ICC, the average age of 48.76 years old, include six cases of adenocarcinoma, All cases were diagnosed by postoperative pathology, None of the patients had received any therapy before the cervical cancer tissue was taken. ICC tumor grade: G1-G2 class: 44 cases, G3 class: 24 cases; clinical stage according to the FIGO standard: stageⅠ_A～Ⅰ_ B: 27 cases, stageⅡ_A: 23 cases, stageⅡ_B and over: 24 cases. 15 cases of normal cervical epithelium (comparison group).1. The expression of Annexin A2, NF-κBp65 and Ki-67 protein were examed by immunohistochemistry in 74 cases of cervical carcinoma, 24 cases of CIN and 15 cases of normal cervical epithelium.2. Statistical analysis was performed by software SPSS10.0 Package. All the test data was separately treated with Chi-square test, correlation analyze, All of the P values resulted from two-sided statistical test. Statistically significant level was considered as "alpha equals 0.05" (a=0.05).Results:1. The protein expression of Annexin A2, NF-κBp65 and Ki67 in different cervical tissues. The positive rate of Annexin A2 expression in normal cervical epithelium, CIN and ICC was 13.3%, 37.5% and 71.6% respectively; The positive rate of NF-κBp65 expression of those was 20%, 33.3%and 74.3%. The positive rate of Ki-67 expression of those was 26.7%, 37.5% and 82.4%. The normal cervical epithelium, as the comparison group, was compared with other groups. The positive rate of Annexin A2, NF-κBp65 and Ki67 expression in ICC was higher than that in normal cervical epithelium and CIN (P=0.00), and no statistical significance was found among normal cervical epithelium and CIN.2. Relationship between the protein expression of Annexin A2, NF-κBp65 and Ki67 and clinicopathological parameters of cervical cancer. The positive rate of Annexin A2 expression in cervical Squamous cell carcinoma and adenocarcinoma was 77.9% and 14.7%, statistical significance was found between the two groups (P=0.00). The positive expression rate of Annexin A2 in grade G1/G2 and grade G3 of ICC was 70.5% and 95.8%, statistical significance was found between the two groups (P=0.01). The positive expression rate of Annexin A2 was higher in cervical cancer with node metastasis than those without (P=0.02). The positive expression rate of Annexin A2 was higher in more than 45-year-old group than those non-more than 45-year-old group (P=0.01), While be independent of clinical stage. The positive expression rate of NF-κBp65 was higher in cervical cancer with node metastasis than those without (P=0.02). The positive expression of NF-κBp65 was independent of factors such as age, tissue types, clinical stage and Pathological grade. The positive expression rate of Ki-67 was higher in more than 45-year-old group than those non-more than 45-year-old group, statistical significance was found between the two groups (P=0.01). The positive expression rate of Ki-67 in grade G1/G2 and grade G3 of ICC was 72.7% and 95.8%, statistical significance was found between the two groups (P=0.02). The positive rate of Ki-67 expression in stageⅠ_A～Ⅰ_B, stageⅡ_A, and stageⅡ_B and over of ICC was 66.7%, 91.3% and 91.7%, statistical significance was found between the three groups (P=0.03). The positive expression of Ki-67 was independent of factors such as tissue types, lymphnode metastasis.3. Correlative analysis showed the expression of Annexin A2 was correlated with the expression of NF-κBp65 and Ki67 in ICC group (r=0.339,0.359,0.542, all P =0.00).Conclusions:1. Annexin A2 is one of important molecular changes in the cervix of the uterus cancer process, its expression is related with the cell's multiplication of cervical cancer, participates in cervical cancer's occurrence, development and metastasis.2. The expression of Annexin A2 may be an auxiliary target which diagnoses as cervical cancer, its expression level to appraises the cervix of the uterus organization's malignant degree and the prognosis has reference value.3. Annexin A2, NF-κBp65, Ki-67 are related with cervical cancer's occurrence and development, and three in cervical cancer's occurrence, the development have the synergism.