Expression And Clinical Implication Of FHIT And MDM2in CIN And Cervical Squamous Cell Cancer

Background and PurposeCarcinoma of the cervix is the second most common gynecological malignancy among women worldwide, whose incidence rate is merely lower than breast cancer. In our country there is a rising trend in incident rate and incidence of young patient with cervical cancer. So far the exact etiology and pathogenesis of cervical cancer remains unknown. The activation of oncogene and inactivation of anti-oncogene is one of mechanisms of tumorigenesis.Fragile histidine triad (FHIT) is one of candidate anti-oncogenes. FHIT plays a role by inducing cell apoptosis and regulating cell cycle and participating in formation of microtubules. The expression of FHIT can affect tumor occurrence and development,also differentiation,invasion and metastasis notablely. Murine double minute2(MDM2) is one of oncogenes. The amplification of mdm2gene and over expression of mdm2protein can regulate P53gene negatively and limit its role as a tumor suppressor, acquired ability of facilitating cell transformation and canceration.This article aims to study the expression of FHIT and MDM2in chronic cervicitis, cervical intraepithelial neoplasia (CIN), cervical squamons cell carcinoma,and their clinicopathologic relationships with cervical squamons cell carcinoma, investigating the role of FHIT and MDM2in occurrence and development of cervical cancer.Materal and Methods1. GroupingAll tissue samples were collected from the department of pathology of the Second Affiliated Hospital of Zhengzhou University from September2009to July2011. They were all embeded in paraffin.50cases of cervical squamous cell cancer and40cases of CIN (including20cases of CIN I and20cases of CINⅡ-Ⅲ) were treated as the experimental groups.20cases of chronic cervicitis tissue which were gained by total hysterectomy because of benign uterine diseases were treated as the control group. None of these patients received treatments with rideotherapy and/or chemotherapy before surgery.2. MethodStreptavidin-peroxidase immunostaining (SP) method was used to detect the expression of FHIT and MDM2in the tissues of chronic cervicitis, CIN and cervical squamons cell carcinoma.3. Statistical analysisAll of the data analysis was performed with statisticial software package SPSS17.0version. Chi-square test was applied in comparing differences between experimental group and control group. Correlation between FHIT and MDM2was analysied by using2x2Contingency Table. The standard statistically significance level was alpha=0.05.Results1. The expression of FHITThe positive expression rates of FHIT displayed a decreasing level from chronic cervicitis group,different CIN groups to cervical cancer group.The positive expression of FHIT in chronic cervicitis tissus was significantly higher than in CIN tissues (χ2=4.335, P<0.05) and cervical squamous cell cancer tissus (χ2=22.256, P<0.05).There was no statistically difference between CIN I and CIN II-III(P>0.05).There was statistically differrence between CIN group and squamous cell cancer group (χ2=12.266, P<0.05). The positive expression of FHIT in cervical squamons cell cancer groups was related to histological grading and lymph node metastasis,(P<0.05), which had nothing to do with the pathological type and age (P>0.05).2. The expression of MDM2The positive expression rates of MDM2displayed a increasing level from chronic cervicitis group,different CIN groups to cervical cancer group. The positive expression of MDM2in chronic cervicitis tissues was significantly lower than in CIN tissues (χ2=5.294, P<0.05)and cervical squannous cellcancer tissus (χ2=22.256, P<0.05). There was no statistically difference between CIN I and CIN Ⅱ-Ⅲ (P>0.05).There was statistically differrence between CIN group and squamous cancer group (χ2=14.042, P<0.05). The expression of MDM2in different cervical squamons cancer groups was not corelated with different ages (P>0.05),but significantly related with clinical stage, histological grade and lymph node mestastasis (P<0.05). The positive expression of MDM2in cervical squamons cell cancer groups was related to pathological type,histological grading and lymph node metastasis,(P<0.05), which had nothing to do with age (P>0.05).3. The correlation between FHIT and MDM2in different cervical squa-mous cell cancer tissuesThe expression of FHIT and MDM2were obviously inverse correlation (χ2=16.563,r=-0.576,P<0.01)Conclusions1. FHIT might play an important role in the occurence of cervical squamous cell carcinoma.2. MDM2might participate in the occurence and development of cervical squamous cell carcinoma.3. Both FHIT and MDM2might participate in the metasitasis of cervical squamous cell carcinoma.4. The FHIT expression was negatively correlated to MDM2expression, indicating that loss expression of FHIT and overexpression of MDM2might promote proliferation and metastasis of malignant tumor.