The Expression And Significance Of IL-17,IL-6,COX-2and TGF-β1Proteins In Cervical Intraepithelial Neoplasia And Cervical Carcinoma

Objective:Cervical carcinoma (cervical cancer) is one of the three most commom gynecologic tumor, ranking after breast cancer and bowel cancer. According to data of the international organization for research on cancer (IARC)2008, there are75000new cases of cervical cancer in China, accounting for14%of the world’s new cases; And the deaths of cervical cancer is up to33000, accounted for12%of all female cancer deaths worldwide. According to a study in2011, new cases of cervical cancer worldwide in the past30years (1980-2010) increased year by year, with an average annual growth rate of0.6%. Cervical intraepithelial neoplasia (CIN) is a general term closely related for a group of premalignant lesions and invasive cervical cancer, including cervical dysplasia and cervical carcinoma in situ, reflects the process of continuous development of cervical cancer, a series of pathological changes from cervical dysplasia to carcinoma in situ and early invasive carcinoma and infiltrating carcinoma. CIN has been accepted by the pathologist and gynecological tumor scholars all over the world. Therefore, to study and clarify the cervical carcinoma, especially the prevention and target molecule mechanism, the development of precancerous lesions of the uterine cervix carcinoma is of great significance to treatment. This research detected the expression level of IL-17, IL-6, COX-2and TGF-β1in cervical cancer and cervical intraepithelial neoplasia tissues, and to analyze the correlation between them, to explore the role of these indexes in cervical cancer and cervical intraepithelial neoplasia in order to judge them as assistant diagnosis and application value in prognosis assessment and treatment and provide help for clinical intervention.Method:Reviewed routine HE slices of cervical conization specimens and cervical cancer specimens,which were from General Department of Pathology in General Hospital of Tianjin Medical University from2009to2013, then selected10cases of normal cervical tissues,90cases of cervical intraepithelial neoplasia(including30cases of CIN Ⅰ,30cases of CIN Ⅱ and30cases of CINⅢ) and30cases of cervical carcinoma.Test the expression level of IL-17, IL-6, COX-2and TGF-β1in each group respectively with immumohistochemistry(IHC) and explore their correlation. The data of this study was analyses using χ2test and Spearman rank correlation.Results:1. There was a significant difference for the expression of IL-17, IL-6, COX-2and TGF-P1in each group. The expression of IL-17, IL-6, COX-2and TGF-β1is increased in normal cervical tissues,cervical intraepithelial neoplasia and cervical cancer(X2=38.210,P<0.01;X2=30.006,P<0.01;X2=35.076,P<0.01;X2=44.161,P<0.01).2. In CIN tissues, the positive expression rate of IL-17, IL-6, COX-2and TGF-pl increased gradually as the CIN lesions level increases. Compared with CIN I and CIN Ⅲ, the positive expression rate of IL-17, IL-6, COX-2and TGF-β1have significant difference (X2=18.515, P=0.001; X2=14.506, P=0.002; X2=14.272, P=0.003; X2=16.223, P=0.001). Compared with CIN I and CIN II, the positive expression rate of IL-17has a significant difference (X2=9.494, P=9.494), and the positive expression rate of IL-6, COX-2and TGF-β1in the comparison of CIN I and CIN Ⅱ, CIN Ⅱ and CINⅡ, there was no significant difference (P>0.05).3. In cervical cancer tissue the expression of IL-6, COX-2and TGF-β1with the increase of surgical pathological staging of cervical caicinoma, the positive expression rate rise, and there was a significant difference compared between I period, Ⅱ period and Ⅲ period(X2=11.607, P=0.03; X2=10.00,P=0.007; X2=11.674,P=0.03).The expression of IL-17with the increase of surgical pathological staging, the positive expression rate rise, but there was no significant difference compared between Ⅰ period, Ⅱ period and Ⅲ period (X2=7.143,P=7.143). The positive expression rate of IL-17, IL-6, COX-2and TGF-β1increases with the increase of histological grade, and there was a significant difference between grade Gland grade G2, G3(X2=10.770, P=0.01; X2=7.873, P=0.049; X2=19.714, P=0.000; X2=10.770, P=0.001).4. The expression of L-17, IL-6, COX-2and TGF-β1were positively correlated(r=0.584, p<0.01and r=0.467, p<0.01and r=0.393, p<0.01), the difference is statistically significant.Conclusion:1. Expression level of1IL-17, IL-6, COX-2and TGF-β1in normal cervical tissues, cervical intraepithelial neoplasia and cervical carcinoma was gradually increased, IL-17, IL-6, COX-2and TGF-β1may be involved in the whole process of cervical cancer occurrence, development and malignant transformation.2. In cervical intraepithelial neoplasia tissue, the positive expression rate of IL-17、 IL-6: COX-2and TGF-β1gradually increased as the level of CIN lesions of increases, and the strong positive rate also increased gradually. There was a significant difference compared between CIN I and CIN III, which means IL-17, IL-6, COX-2and TGF-β1can be used as a new immunological indexes to evaluate low level with high level cervical intraepithelial neoplasia lesions.3. In cervical cancer tissue, the positive expression rate of IL-17, IL-6, COX-2and TGF-β1increased with the elevated of operation pathologic staging, And with the histological grade increased, IL-17, IL-6, COX-2and TGF-β1expression rate increased. IL-17, IL-6, COX-2and TGF-β1expression may be one of important factors in the occurrence and development of cervical squamous cell carcinoma, malignant evolution mechanism in cervical squamous cell carcinoma.4. The expression of L-17, IL-6, COX-2and TGF-β1in normal cervix, cervical intraepithelial neoplasia and cervical carcinoma were positively correlated.