Expression And Clinical Significance Of SULT1E1 In Ovarian Serous Tumors

ObjectiveThe mortality rate of malignant ovarian tumor is the highest in gynecological malignancies,It becomes a main tumor which threat women's lives and health of. Though it has been made some progress on the means and methods of diagnosis and treatment of Ovarian cancer in recent years,no significant improvement in their mortality.It is known to all that ovary is an important target organ of estrogen.A mount of research suugest the pathological basis of estrogen in ovarian cancer.Some studies has confirmed that estrogen metabolites can combined with DNA,then start the procession of canceration.Sulfotransferase(SULTs) superfamily including SULT1 and SULT2.Human estrogen sulfotransferase,hEST,also called SULT1E1 is one of the main members of the SULT1 family,which is the strongest enzyme of the 10 known isoforms catalyzing estrogen at present,which catalyzes the transfer of sulfonate radical(SO3-)to the 3-hydroxyl group.As an important disintoxicating enzyme, SULT1E1 catalyzes the sulfation of estrone and estradiol with extremely high efficiency,detoxification by which a relatively hydrophobic xenobiotic is biotransformed into a more water-soluble sulfuric ester,reducing the level of estrogen exposion in the circulation and the target organization.Studies demonstrated that decreased SULT1E1 expression may result in estrogen-dependent tumor developing.However,the relationship between estrogen sulfotransferase and ovarian serous tumors has not been examined.The aim of this study was used Reverse transcription - polymerase chain reaction(RT-PCR),immunoblotting(Western-Blot), immunohistochemistry to investigate the expression of human estrogen sulfotransferase mRNA and protein in ovarian serous tumors,to investigate the relationship among SULT1E1'mRNA,protein and pathological parameters of ovarian serous cystadenocarcinoma.To understand the relationship between the expression of SULT1E1 mRNA,protein and the occurrence and development of ovarian serous tumors.Materials and MethodsIn this study,60 samples were chosen from normal ovary and ovarian serous tumors who suffered from hysterectomy at Department of Gynecology and Obsterics, Shengjing Hospital of China Medical University,from 2007-6 to 2008-3.They had been diagnosised correctly by routine pathological examination.None of the patients had received radiotherapy,chemotherapy,hormonal therapy and other treatment before operation.The full clinical data had been collected.To inspect the protein expression of SULT1E1 mRNA and protein in nomal ovary,ovarian serous cystadenoma,ovarian borderlineserous cystadenoma,ovarian serous cystadenocacinoma of by RT-PCR,Western blot and immunohistochemistry test.Taking normal ovary as control,and compare the differences in different tissues.SPSS 13.0 software was employed to analyze all data.Differences in relative content using One Way ANOVA,LSD-test, Two-Independent-Samples-test method.The expression rate of the four different ovarian tissues use chi-square test or Fisher's exact probability method.P＜0.05 was considered as statistical significance.ResultsThe expression rate and relative content of SULT1E1 mRNA(43.3%,0.35±0.05) in serous cystadenocacinoma were lower than those in nomal ovary(9/10,1.07±0.06), the differences had stastistical significance(P＜0.05).The relative content of SULT1E1 mRNA in serous cystadenocacinoma(0.35±0.05) was lower than those in ovarian borderline serous cystadenoma(0.73±0.02) and ovarian serous cystadenoma(0.76±0.05),and the differences had stastistical significance(P=0.000).The relative content of SULT1E1 mRNA in ovarian borderline serous cystadenoma and ovarian serous cystadenoma were lower than those in nomal ovary,and the differences had stastistical significance(P=0.000).Compared the expression rate and relative content of SULT1E1 mRNA between early stage(Ⅰ+Ⅱ) serous cystadenocacinoma(3/7,0.35±0.07) and late stage(Ⅲ+Ⅳ) serous cystadenocacinoma(43.5%,0.35±0.04),the differences had no stastistical significance(P＞0.05).Compared the expression rate and relative content of SULT1E1 mRNA in G1(4/7,0.36±0.03),G2(4/10,0.35±0.05)and G3(38.5%, 0.34±0.06),the differences had no stastistical significance(P＞0.05).With and without ascites,the expression rate and relative content(42.9%,0.35±0.05;43.8%,0.35±0.04) of SULT1E1 mRNA had no stastistical significance(P＞0.05).Compared the expression rate and relative content of SULT1E1 mRNA with lymph metastasis (36.4%,0.36±0.05)and without lymph metastasis(47.4%,0.35±0.05),the differences had no stastistical significance(P＞0.05).By Western-Blot,we can find that the expression rate and relative content of the SULT1E1 protein in ovarian serous cystadenocacinoma(43.3%,0.24±0.06) are lower than those in nomal ovary(9/10,1.19±0.05),the differences have stastistical significance(P＜0.05).The relative content of SULT1E1 protein(0.24±0.06) in serous cystadenocacinoma was lower than those in ovarian borderline serous cystadenoma(0.71±0.03) and ovarian serous cystadenoma(0.75±0.04),the differences had stastistical significance(P=0.000).The relative content of SULT1E1 protein in ovarian borderline serous cystadenoma and ovarian serous cystadenomawere lower that that of nomal ovary,the differences had stastistical significance(P=0.000).Compared the expression rate and relative content of SULT1E1 protein between early stage (Ⅰ+Ⅱ) serous cystadenocacinoma4/7,0.25±0.06) and late stage(Ⅲ+Ⅳ) serous cystadenocacinoma((39.1%,0.24±0.07),the differences had no stastistical significance (P＞0.05).Compared the expression rate and relative content of SULT1E1 protein in G1(4/7,0.25±0.05),G2(3/10,0.25±0.06)and G3(46.2%,0.23±0.08),the differences had no stastistical significance(P＞0.05).With and without ascites,the expression rate and relative content((50.0%,0.25±0.06;37.5%,0.24±0.07) of SULT1E1 protein had no stastistical significance(P＞0.05).Compared the expression rate and relative content of SULT1E1 protein with lymph metastasis(45.5%,0.21±0.07) and without lymph metastasis(42.1%,0.26±0.05),the differences had no stastistical significance (P＞0.05).By Immunohistochemistry,we can find that the SULT1E1 protein expressed in cytoplasm.The expression rate of the SULT1E1 protein in ovarian serous cystadenocacinoma(43.3%)was lower than that in nomal ovary(9/10),the differences had stastistical significance(P=0.013).The differences of the expression rate in other groups had no stastistical significance(P＞0.05).Compared the expression rate of SULT1E1 protein between early stage(Ⅰ+Ⅱ) serous cystadenocacinoma(3/7)and late stage(Ⅲ+Ⅳ) serous cystadenocacinoma(39.1%),the differences had no stastistical significance(P＞0.05).Compared the expression rate and relative content of SULT1E1 protein in G1(4/7),G2(3/10)and G3(46.2%),the differences had no stastistical significance(P＞0.05 ).With and without ascites,the expression rate(50.0%;37.5%) of SULT1E1 protein had no stastistical significance(P＞0.05 ).Compared the expression rate of SULT1E1 protein with lymph metastasis(45.5%) and without lymph metastasis(42.1%),the differences had no stastistical significance(P＞0.05).Conclusions1.The SULT1E1 protein of the four ovarian tissues express in cytoplasm.2.The expression rate and relative content of SULT1E1 mRNA and protein in ovarian serous cystadenocarcinoma are lower than those of in nomal ovary,the differences are significant(P＜0.05).The relative content of SULT1E1 mRNA and protein in ovarian serous cystadenoma,borderline ovarian serous cystadenoma were lower than those of ovarian serous cystadenocarcinoma,the differences were significant(P＜0.05).In all,the low expression of SULT1E1 mRNA and protein were related to the occurrence and development of ovarian serous cystadenocarcinoma.To inspect the express of SULTEmRNA and protein;in ovary tissues may be used to diagnose and identification diagnosed the ovarian serous tumors.3.The expression of SULT1E1 mRNA and protein are not related to surgical pathologicstage,cell differentiation,.ascites and lymph metastasis(P＞0.05).