Their Clinical Significance Of FOXM1and GLi-1Proteins In High-Grade Serous Carcinoma

Obiective: To detect and valueatethe difference of FOXM1, Gli-1 expression in normal fallopian tube,high-grade serous carcinoma,(HGSC).To valuate the relationship between FOXM1, Gli-1 overexpression and clinicopathologic features of the patients.Investigate the relationship between FOXM1, Gli-1 and PCNA.Evaluate the relevance of FOXM1, Gli-1 expression to the prognosis of high-grade serous carcinoma.Methods: The study include 50 patients who had presented for treatment of high-grade serous carcinoma the second affiliated hopital of Hebei medical university between June 2003 and Jan. 2011.The patients had neoadjuvant chemotherapy radiotherapy before surgical staging,the tumors were complete clinial information and follow-up.20 normal fallopian tube tissue were selected as control.The protein expression FOXM1, Gli-1were detected in high-grade serous carcinoma immunohistochemistry Elivision plus three-step,Negative control was carried out in identical condition excluding PBS, instead of antibody. The immunocytochemistry(IHC)procession was also carried out according to manufacturer’sinstructions.A followed-up test was carried out in 50 patients high-grade serous carcinoma.We determined the cut-off point were 36 and 60 months.We calculated the the sum survival rates in 3 and 5 years and The correlation between the factors whichwere clinical FOXM1, Gli-1, age stage,pathological grade,lymph node metastasis were screened,and the risk coefficient of independent factors were determined.The statistics analysis were carried out by SPSS13.0 statistical package. In the study,categorical data were analyzed using Chi-square test,FOXM1, Gli-1 differences in different clincal pathological indicators were analyzed using Chi-square test or Fisher’s exact test.Spearmanrankcorrelationwas used to analysis the correlation of FOXM1, Gli-1 and PCNA.Single factor and Cox multivariatesurvival analysis o prognostic factors in patients with high-grade serous carcinoma.Kaplan-Meierunivariate survival analysis was used to draw survival curve,calculate the survival rate of the patients.Log-Rank test was used to compare the significant different of survival rate and P-values<0.05 were considered statistically significant.Rusults: 1 The expression of FOXM1, GLi-1 and PCNA in high-grade ovarian serous adenocarcinoma and normal fallopian tube tissues. 1.1 FOXM1 protein expressionThe result of IHC showed that the positive rates of FOXM1 protein expression in high-grade ovarian serous adenocarcinoma were 84%, significantly higher than that 0% in normal fallopian tube tissues(P<0.05). 1.2 GLi-1 protein expressionThe result of IHC showed that the positive rates of GLi-1 protein expression in high-grade ovarian serous adenocarcinoma were 78%, significantly higher than that 10% in normal fallopian tube tissues(P<0.05). 1.3 PCNA protein expressionThe result of IHC showed that the positive rates of PCNA protein expression in high-grade ovarian serous adenocarcinoma were 68%, significantly higher than that 15% in normal fallopian tube tissues(P<0.05). 2 relationship between FOXM1, GLi-1 and clinicpathological characteristics in high-grade ovarian serous adenocarcinomaThe significantly differences of FOXM1, GLi-1 protein expression were not found in age,and distant metastasis. The significantly differences of FOXM1, GLi-1 protein expression were found in FIGO stage. 3 The correlation between FOXM1, GLi-1 and PCNA protein in high-grade ovarian serous adenocarcinoma 3.1 The correlation between FOXM1 and GLi-1 protein expressionIn the FOXM1 high expression of 42 cases,36 cases Gli-1 have high expression, FOXM1 and Gli-1 has a significant correlation(r=0.427 P<0.05). 3.2 The correlation between FOXM1 and PCNA protein expressionThere was a significant positive correlation between FOXM1 and PCNA expression(r=0.402 P<0.05) in high-grade ovarian serous adenocarcinoma. In which tumors with high PCNA expression had a significantly higher expression of FOXM1(P<0.05). 3.3 The correlation between between Gli-1 and PCNA protein expressionThere was no correlation between Gli-1 and PCNA expression(r=0.05 P>0.05)in high-grade ovarian serous adenocarcinoma, in which tumors with high PCNA expression had a no significantly higher expression of Gli-1( P>0.05). 4 Prognosis in high-grade ovarian serous adenocarcinoma. 4.1 The relationship between FOXM1, GLi-1and prognosis in high-grade ovarian serous adenocarcinomaAccording to the result of IHC and follow-up date, the survival rates of 3 and 5 years were( 23.8% 87.5%) and in high-grade ovarian serous adenocarcinoma with FOXM1 high expression, significantly lower than(4.8% 50.0%) in patients with FOXM1 low expression.According to the result of IHC and follow-up date, the survival rates of 3 and 5 years were( 25.6% 63.6%) in high-grade ovarian serous adenocarcinoma with GLi-1 high expression, significantly lower than(5.1% 36.4%)in patients with GLi-1 low expression. 4.2 The relationship between clinicpathological characteristics and prognosis in high-grade ovarian serous adenocarcinomaAccording to the result of IHC and follow-up date, the survival rates of 3 and 5 years were(21.9% 0)and in high-grade ovarian serous adenocarcinoma with FIGO(Ⅲ/Ⅳ), significantly lower than(55.6% 33.3%) in patients with FIGO(Ⅰ/Ⅱ).According to the result of IHC and follow-up date, the survival rates of 3 and 5 years were(0 0)in high-grade ovarian serous adenocarcinoma with distant metastasis, the survival rates of 3 and 5 years were(41.5% 14.6%)in high-grade ovarian serous adenocarcinoma with no distant metastasis 3 year and the 5-year survival rate was statistically significant difference(P<0.05). 5 COX multivariate survival analysis of high-grade ovarian serous adenocarcinomaIn univariate and multivariate survival analyses,high level of FOXM1, FIGO stage was identified as an independent factor poor prognosis in patients with high-grade ovarian serous adenocarcinoma.Conclusion:1 The protein expression of FOXM1 and Gli-1in HGSC group was much higher than that in normal fallopian tube group.And the expression of FOXM1 and Gli-1 positively correlated with FIGO stage.While not statistically different indifferent ages,lymph nodes metastasis in HGSC patients.So FOXM1 maybe contribute to carcinogenesis,progression,invasion and metastasis of HGSC.2 A significant positive correlation was found between the expression of protein FOXM1 and protein Gli-1 and PCNA in HGSC.This suggested that FOXM1 may have some synergistic effect during the occurrence and development process in HGSC.FOXM1 contribute to progression.3 FOXM1 protein expression and Gli-1 of 3 and 5 years survival rate significantly decreased, prompt high expression is both factors that affect the prognosis of patients with high levels of serous adenocarcinoma4 In univariate and multivariate survival analyses,high level of FOXM1, FIGO stage was identified as an independent factor poor prognosis in patients with HGSC.