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The Expression And Clinical Significance Of Cripto-1, P-AKT And PTEN In Cervical Carcinoma

Posted on:2017-02-13Degree:MasterType:Thesis
Country:ChinaCandidate:Y X YuFull Text:PDF
GTID:2284330485985455Subject:Obstetrics and gynecology
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The Cervical cancer is the second most common cancer in women worldwide, where cervical cancer is the third leading cause of cancer death in women. The global yearly incidence of cervical cancer in 2012 was 527,600; the annual death rate was 265,700. An estimated 444,500 new cases of carcinoma of the uterine cervix were diagnosed in the developing countries in 2012, and 230,200 people died of the disease. Immunization against HPV prevents infection with the types of HPV against which the vaccine is designed and, thus, is expected to prevent specific HPV cancer in women. Cervical cancer is decreasing in the United States because of the wide use of screening; however, it is increasing in developing countries (with 84.2% of cases occurring in developing countries), because screening is not available to women in developing countries. However, cervical cancer is a major world health problem for women.Epidemiological studies have found that HPV infection was closely related to the incidence of cervical cancer, particularly high-risk HPV (HPV 16 and HPV 18) infection. There are other factors related to cervical cancer in addition to HPV infection, from HPV infection, cervical intraepithelial neoplasia to invasive Carcinoma of Cervix, the pyramid of distribution indicate that in the development of cervical cancer HPV infection is not the only independent risk factor. Numerous studies have shown that mutations are the radical cause in the development of malignant tumors, as with other cancers, cervical cancer is also known as oncogene activation and inactivation of tumor suppressor genes for multiple stage and multiple-step development process. Therefore, molecular target therapy of cervical cancer remains a top priority.Cripto-1 is a member of the epidermal growth factor family. And there is a very high correlation of tumor in a variety of cancer cell lines, Besides the Cripto-1 expression is abnormally high in cancer, and low in normal adult tissues or none. Cripto-1 in cancer occurrence, played an important role in the process of cancer growth, malignant transformation and metastasis, is recognized as the oncogene. PTEN is the 10th loss of chromosome homology gene of protein phosphatase-tension, also known as MMACI, is a tumor suppressor gene which found in 1997, is the first ever found with a dual-specificity phosphatase activity of tumor suppressor genes. PTEN inhibit tumor cells by its development, invasion and metastasis, by regulating the intracellular signal transduction pathways involved in normal physiological and pathological processes.ObjectiveUsing the Immunohistochemistry method and Western blot to explore the expression of Cripto-1, p-AKT and PTEN in different cervical tissues (such as normal cervical epithelium, cervical intraepithelial neoplasia, invasive carcinoma of cervix), and to analysis of whether there is significant, and its relevance. Considering the relationship between expression and the clinical and pathological features, analyzing and provides a theoretical basis for diagnosis and treatment.Material and Methods1. Immunohistochemistry method was used to explore the positive rate of Cripto-1, p-AKT and PTEN in the 35 ICC cases, the 30 CIN cases and the 30 NCE cases. These datas were analysised the correlation. Then we will assess the association between expression of Cripto-1, p-AKT and PTEN with clinicopathologic parameters.2. Western blot was also used to explore the expression levels of Cripto-1, p-AKT and PTEN in the 35 cases of ICC, the 30 cases of CIN and the 30 cases of NCE.3. All the quantitative data was expressed in Mean ± standard deviation (x± s),and the qualitative information was expressed as rate.x2 test was used between Cripto-1, p-AKT and PTEN and its clinical pathological features. The correlation between Cripto-1, p-AKT and PTEN was analysised by Spearman test, P<0.05 and the difference was statistically significant.Results1. Immunohistochemistry method showed that the positive rate of Cripto-1, p-AKT in 35 ICC cases (60.0%,80.0%) is significantly higher than that in 30 cases CIN tissues (42.9%,40.0%) and 30 cases NCE tissues (3.3%,10.0%) (P<0.05) PTEN was 90.0%(27/30) respectively in 30 cases NCE tissues, but significantly lower in CIN (60.0%) and NCE (28.6%) (P<0.05)2. Western blot showed that the expression level of Cripto-1, p-AKT in ICC tissues (0.83±0.21,0.67±0.23) was obviously higher than that in CIN(0.33± 0.06,0.33±0.13) and in NCE (0.08±0.03,0.11±0.05) respectively, P<0.05, and it in CIN was higher than that in NCE (P<0.05) respectively. PTEN in NCE (0.10±0.05) was obviously higher than that in CIN (0.31±0.13) and ICC (0.81±0.26) respectively, P<0.05, and it in CIN was higher than that in ICC cases (P<0.05) respectively.3. Immunohistochemical results of correlation analysis found that Cripto-1 were positively correlated with p-AKT, Cripto-1 protein was negatively correlated with PTEN protein and PTEN protein and p-AKT protein was negatively correlated. The expression of Cripto-1 protein in ICC was correlated to lymph node metastasis (P <0.05),but there was no correlation to the patients’age,histological type, clinical stage (P>0.05); the expression of p-AKT and PTEN protein was no correlated to lymph node metastasis in the 35 cases of ICC, patients’age, histological type, clinical stage (P>0.05)Conclusion1. The expression of Cripto-1, p-AKT protein obviously increased in ICC, and the expression of PTEN obviously decreased in ICC, there was a significant difference between NCE and CIN.2. There was relationship between the expression of Cripto-1 and lymph node metastasis significantly, it showed that Cripto-1 may play an important role in the prognosis of cervical carcinoma Ib-IIa.3. The Cripto-1 and p-AKT and PTEN protein could be used as tumor markers for the prognosis of early cervical carcinoma (such as Ib-IIa stage).
Keywords/Search Tags:Immunohistochemistry, Western blot, Cripto-1, p-AKT, PTEN, Cervical carcinoma
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