| Objective: Epithelial ovarian cancer is the most common histological type of ovarian tumor, accounts for primary ovarian tumors 50%~70%, ovarian malignant tumor 85%~90%. In malignant tumors of female genital tumor,The epithelial ovarian tumor has the highest fatality rate. The types of ovarian serous carcinoma include serous ovarian carcinoma, mucinous carcinoma, endometrioid carcinoma, clear cell carcinoma, transitional cell carcinoma. Serous ovarian cancer is the most common type of ovarian tumors, accounting for 40-60% of epithelial ovarian cancer. In recent years, through morphological, molecular biology and other studies suggest that the dualism of ovarian cancer model can be used to ovarian serous adenocarcinoma well. The low-grade ovarian serous adenocarcinoma is a process, through the pathogenesis of benign, borderline and malignant tumor. High-grade ovarian serous adenocarcinoma directly derived from the ovarian surface epithelium, some studies show that high-grade ovarian serous adenocarcinoma can originate from the fallopian tube.As a genetic disease, the occurrence and development process of ovarian serous carcinoma is based on abnormal gene, involving oncogene activation and anti-oncogene inactivation. Overall, the biological behavior of ovarian serous carcinoma is a kind of multi-step and multi-factor.PHLPP is a tumor suppressor gene, expressed in many kinds of tumors, such as ovarian cancer, breast cancer, colorectal cancer, malignant glioma. The study demonstrated that, in the PI3K-Akt signaling pathway,the protein PHLPP dephosphorylated the hydrophobic groups of Akt, so as to cause the inhibition of the PI3 KAkt signaling pathway and realize the negative regulatory factor of Akt and its downstream. As an important signaling molecule downstream of Akt in PI3K-Akt signaling pathway, FoxO3 a has a close relationship with the occur- rence and development of tumor. As an important member of the FOXO family, FoxO3 a participates in cell proliferation, differentiation, development and angiogenesis by regulating the transcription of target genes. Foxo3 a widely exists in the human organization, such as colon, breast, stomach, ovary and other tissues. In the PI3K-AKT signaling pathway,AKT phosphorylates FoxO3 a that can promote the development of tumor through the regulation of downstream genes. As an DNA double-strand break repair gene, RAD51 is one of the important downstream molecules of FoxO3 a. The protein RAD51 is the key enzyme of homologous recombination repair. In recent years, the studies found that the expression of Rad51 increasein many tumor tissues, such as: breast cancer, colon cancer, ovarian cancer, etc, which resulting in homologous recombination capacity and the gene instability increases, resulting in the recombinational repair of cells out of control, apoptosis, gene mutation etc. There is a close relationship between RAD51 and the occurrence and development of tumor. In this study, based on immunohistochemistry three-step method and the ovarian dualism model, we Detect the expression of PHLPP、FoxO3a and RAD51 protein in high-grade and low-grade ovarian serous adenocarcinoma, Serous borderline cystadenoma, Serous cystadenoma, Normal ovary and normal fallpion tube. In order to further explore the pathogenesis of high-grade and low-grade ovarian serous carcinoma, and provide reference evidence for prognosis and treatment of ovarian serous carcinoma.Methods:The 145 epithelial ovarian cancers collected from patients diagnosed between 2006 and 2011 at the Second Hospital of Hebei Medical University. Those northern Han women with complete clinical data are first time for surgical treatment, without any chemotherapy and radiotherapy before operation and resected and pathologically confirmed. The 145 epithelial ovarian cancers include 46 cases of high-grade ovarian serous adenocarcinoma, 26 cases of low-grade ovarian serous adenocarcinoma, 21 cases of Serous borderline cystadenoma, 35 cases of serous cystadenoma, 9 cases of normal ovary and 8 cases of normal fallpion tube. Using immunohistochemistry three-step method to Detect the expression of PHLPP、FoxO3a and RAD51 protein in high-grade and low-grade ovarian serous adenocarcinoma, serous borderline cystadenoma, serous cystadenoma, normal ovary and normal fallpion tube. In the whole experiment process in strict accordance with the instructions of three step immunohistochemical kit, With phosphate buffer(PBS) instead of primary antibody as negative control and the positive biopsy known as positive control. Using SPSS21.0 software to analysis statistical. Using The chi square test to analysis count data. Using single factor analysis of Kaplan-Meier to draw survival curves corresponding and calculate survival rate. Using multivariate Cox to analysis the prognostic factors of high grade ovarian serousadenocarcinoma patients. Using Log-rank test to compare the different of survival rate.α=0.05.Results:1 Expressions of PHLPP in different grades ovarian serous adenocarcinoma and the effect of PHLPP expression on prognosisThe expressions of PHLPP in high-grade ovarian serous adenocarcinoma, normal fallpion tube, low-grade group, serous borderline cystadenoma, serous cystadenoma, normal ovary were 11/46, 6/8, 6/26, 16/21, 32/35, 9/9,the positive expression rates were 23.9%, 75.0%, 23.1%, 76.2%, 91.4%, 100%. The statistical analysis showed that the positive expression rates of PHLPP in high-grade group was significantly lower, compared with normal fallpion tube(P<0.05). The positive expression rates were significant difference between low-grade group and serous borderline cystadenoma, serous cystadenoma and normal ovary(P<0.05). The other groups was not statistically difference. The positive expression rates were not statistically difference in low-grade and high-grade groups(P>0.05).In 46 cases of high-grade ovarian serous adenocarcinoma, PHLPP negative expression of 3 year and 5 year survival rates were 32.0% and 8.0%. PHLPP positive expression of 3 year and 5 year survival rates were 37.5% and 12.5%. Statistical analysis showed that the 3 and 5 years survival rates of PHLPP negative and positive expression were not statistically difference(P>0.05). In 26 cases of low-grade group, the 3 and 5 years survival rates of PHLPP negative expression were 58.3% and 16.7%. PHLPP positive expression of 3 and 5 year survival rates were 80.0% and 60.0%. Statistical analysis showed that the 3 and 5 years survival rates of PHLPP negative and positive expression were not statistically difference(P>0.05).2 Expressions of FoxO3 a in different grades ovarian serous adenocarcinoma and the effect of FoxO3 a expression on prognosisThe expressions of FoxO3 a in high-grade ovarian serous adenocarcinoma, normal fallpion tube, low-grade group, serous borderline cystadenoma, serous cystadenoma, normal ovary were 12/46, 6/8, 7/26, 13/21, 29/35, 9/9,the positive expression rates were 26.1%, 75.0%, 26.9%, 61.9%, 82.9%, 100%. The statistical analysis showed that the positive expression rates of FoxO3 a protein in high-grade group was significantly lower, compared with normal fallpion tube, the difference was statistically significant(P<0.05). The positive expression rate in low-grade group was significant lower then serous borderline cystadenoma, serous cystadenoma and normal ovary, the positive expression rate in serous borderline cystadenoma was also significant lower then normal ovary(P < 0.05). The positive expression rates were not statistically difference in low-grade and high-grade groups(P>0.05).In 46 cases of high-grade group, FoxO3 a positive expression of 3 year and 5 year survival rates were 57.1% and 28.6%. the 3 year and 5 year survival rates of FoxO3 a negative expression were 26.9% and 3.8%. Statistical analysis showed that the 3years survival rates of FoxO3 a negative and positive expression were not statistically difference(P>0.05), the 5 years survival rates of FoxO3 a positive expression were statistically higher then negative expression groups(P<0.05). In 26 cases of low-grade group, the 3 and 5 years survival rates of Fox O3 a positive expression were 83.3% and 66.7%. the 3 and 5 years survival rates of FoxO3 a negative expression 55.6% and 0%. Statistical analysis showed that the 3 years survival rates of FoxO3 a negative and positive expression were not statistically difference(P>0.05), the 5 years survival rates of FoxO3 a positive expression were statistically higher then negative expression groups(P<0.05).3 Expressions of RAD51 in different grades ovarian serous adenocarcinoma and the effect of RAD51 expression on prognosisThe expressions of RAD51 in high-grade ovarian serous adenocarcinoma, normal fallpion tube, low-grade group, serous borderline cystadenoma, serous cystadenoma, normal ovary were 33/46, 1/8, 17/26, 10/21, 9/35, 2/9,the positive expression rates were 71.7%, 12.5%, 65.4%, 47.6%, 25.7%, 22.2%. The statistical analysis showed that the positive expression rates of RAD51 protein have significantly different between high-grade ovarian serous adenocarcinoma and normal fallpion tube(P < 0.05). The positive expression rates were significant difference between low-grade group and normal ovary, low-grade group and serous cystadenoma(P < 0.05). The positive expression rates were not statistically difference in low-grade and high-grade groups(P>0.05).In 46 cases of high-grade group, the 3 and 5 years survival rates of RAD51 positive expression were 25.0% and 4.2%. the 3 and 5 year survival rates of RAD51 negative expression were 55.6% and 22.2%. Statistical analysis showed that the 3 and 5 years survival rates of RAD51 positive expression were statistically lower then negative expression groups(P<0.05). In 26 cases of low-grade group, the 3 and 5 years survival rates of RAD51 positive expression were 55.7% and 11.1%. The 3 and 5 year survival rates of RAD51 negative expression were 85.7% and 57.1%. Statistical analysis showed that the 3 years survival rates of RAD51 positive and negative expression were not statistically difference(P>0.05), the 5 years survival rates of RAD51 negative expression were statistically higher then positive groups(P<0.05).4 The Cox multivariate survival analysis of different grades of ovarian serous adenocarcinomaThe Cox multi factor survival analysis of different grades of ovarian serous adenocarcinoma included PHLPP, FoxO3 a and RAD51, age, metastasis, clinical stage, chemotherapy. We discover that in high-grade groups, chemotherapy entered the Cox proportional hazards regression mode. Chemotherapy was an independent prognostic factor for high-grade ovarian serous adenocarcinoma. In low-grade groups, there were no facters entered the Cox proportional hazards regression model.Conclusions:1 In high-grade ovarian serous adenocarcinoma, the positive expression rates of PHLPP and FoxO3 a protein were lower then normal fallpion tube, the positive expression rates of RAD51 protein were higher then normal fallpion tube,showed that three genes might be participated in the occurrence of highgrade serous ovarian adenocarcinoma.2 In low-grade ovarian serous adenocarcinoma, serous borderline cystadenoma, serous cystadenoma, normal ovary, the expressions of PHLPP and FoxO3 a protein were increased gradually, the expression of RAD51 protein were decreased gradually. The three genes might be involved in the pathogenesis of low-grade ovarian serous adenocarcinoma.3 The expressions of PHLPP,FoxO3 a and RAD51 protein in low-grade and high-grade ovarian serous adenocarcinoma were not statistically difference, suggested that there are many common molecular basis for the occurrence of high-grade and low-grade ovarian serous adenocarcinoma.4 PHLPP had no significant difference in the prognosis of high and low grade groups, FoxO3 a had long effect on the survival rates of high-grade groups and low-grade groups, RAD51 has a certain value in judging the prongosis of high-level and low-grade groups.5 In high-grade ovarian serous adenocarcinoma, chemotherapy entered the Cox proportional hazards regression mode. In low-grade ovarian serous adenocarcinoma, there were no facters entered the Cox proportional hazards regression model. |
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