the cancer antigen 125 ( ca-125 ) is a transmembranaire glycoprotein with a high molecular weight of > 200 kd . ca-125 derives its numeric designation from its monoclonal antibody oc-125 , which was generated by immunization of balb / c mice with the ovca43 cell line isolated from ascites fluid of a patient with serous papillary cystadenocarcinoma of the ovary in 1981 . this glycoprotein is expressed normally in fetal coelomic epithelium , by epithelial ovarian tumors , normal and pathologic tissues of mllerian duct origin , and mesothelial cells . although serum ca-125 levels have been used as a valuable tumor marker for the diagnosis of epithelial ovarian cancer and the detection of recurrence after primary treatment , its role is controversial in endometrial cancer ( ec ) as a useful tumor marker . a number of studies have reported that serum ca-125 levels were important for preoperative diagnosis and prediction of disease recurrence , and their elevation correlated with advanced - stage ec [ 6,915 ] . nevertheless , the inconsistency between serum ca-125 levels and the extent of disease or prognosis still exists in ec because most related studies had some limitations such as a small number of patients and various histological types [ 13,1619 ] . in several reports , the serum ca-125 levels seem to be increased in the majority of patients with advanced disease but only in about 1020% of patients with stage i ec . however , no such correlation between ca125 levels and extent of disease has been observed in other reports . there are few studies on the detection of endometrial ca-125 expression as a tumor marker of ec [ 2124 ] . large - scale and long - term studies are required to evaluate the role of serum ca-125 levels for predicting prognosis in ec because most of patients have early - stage diseases cured by surgery alone . there have been only few studies on the detection of ca-125 in cervical and vaginal secretions in healthy women and women with endometrial diseases . .   first observed very high levels of ca 125 in cervical mucus from women with regular menstrual cycles and this was confirmed by martinez et al . . we have recently reported that ca125 was detected in cervical and vaginal secretion of healthy chinese women using the automatic electro - chemiluminescent immunoassay . in this study , we further investigated the ca-125 levels in cervical and vaginal secretions from chinese patients with endometrial polyps , hyperplasia and carcinoma in comparison with those in endometrium and serum . a total of 254 subjects were recruited into this study from january 2005 to december 2009 and they were classified into six groups , namely proliferative phase endometrium ( n=24 ) , secretory phase endometrium ( n=29 ) , non - functional endometrial polyps ( n=24 ) , simple hyperplasia ( n=24 ) , complex hyperplasia ( n=26 ) , and endometrial carcinoma ( n=126 ) . among 148 women from these subjects , the diagnosis of these diseases was based on the criteria of international classification of diseases ( icd ) version 11 . formalin - fixed hematoxylin & eosin - stained 6-m slides from the endometrial tissue of all subjects were performed and revised by two senior pathologists in order to verify the diagnosis . this study was approved by the ethics committee of xiaolan hospital affiliated to southern medical university , zhongshan , china . electro - chemiluminescent immunoassay was used to determine the ca-125 levels in serum and cervical and vaginal secretions using an automatic elecsys 2010 analyzer ( roche diagnostics , indianapolis , in ) . the limit of detection was determined by analyzing 10 replicates of the zero calibrator and 4 replicates of the lowest nonzero calibrator ( 15 u / ml ) . the limit of detection for ca-125 in human serum , and cervical and vaginal secretions was determined to be 0.50 u / ml . the precision and accuracy were within 12% in terms of coefficients of variation ( cvs ) for the low and high controls ( 35 and endometrial ca-125 was detected by immunohistochemical technique ( elivision plus ) using a commercially available kit ( maixin bio , fuzhou , china ) . four-m unstained slides were prepared from each case for immunohistochemical staining for anti - ca125 antigens with clone ov 125 diluted 1:2 . immunohistochemistry was performed by deparaffinization of slides in xylene , absolute ethyl alcohol , and degradated alcohols 96% and 70% . immunoperoxidase stains were performed using a modified labeled streptavidin technique and run on an automated system using a commercially available chromogen . the percentage of tissue area stained in 1012 high power fields and its intensity scored as 0 , 1 , 2 , and 3 . cancer tissue with staining of more than 50% of the area examined and an intensity of 2 and 3 was considered as positive ( score 1 ) . pathologic grading of the tumor cells was done according to the 1988 figo grading system . the tumor was graded based on the percentage of solid non - squamous growth as follows : grade 1 , 5% solid growth ; grade 2 , 650% solid growth ; grade 3 , > 50% solid growth . the overall grade of architecturally grade 1 or grade 2 tumors was increased by one if there was notable nuclear atypia . differences among groups of subjects were compared by the  or fisher s exact test . correlation analysis was performed to determine the relationship between the ca-125 levels measured in different biological matrices a total of 254 subjects were recruited into this study from january 2005 to december 2009 and they were classified into six groups , namely proliferative phase endometrium ( n=24 ) , secretory phase endometrium ( n=29 ) , non - functional endometrial polyps ( n=24 ) , simple hyperplasia ( n=24 ) , complex hyperplasia ( n=26 ) , and endometrial carcinoma ( n=126 ) . among 148 women from these subjects , the diagnosis of these diseases was based on the criteria of international classification of diseases ( icd ) version 11 . formalin - fixed hematoxylin & eosin - stained 6-m slides from the endometrial tissue of all subjects were performed and revised by two senior pathologists in order to verify the diagnosis . this study was approved by the ethics committee of xiaolan hospital affiliated to southern medical university , zhongshan , china . electro - chemiluminescent immunoassay was used to determine the ca-125 levels in serum and cervical and vaginal secretions using an automatic elecsys 2010 analyzer ( roche diagnostics , indianapolis , in ) . the limit of detection was determined by analyzing 10 replicates of the zero calibrator and 4 replicates of the lowest nonzero calibrator ( 15 u / ml ) . the limit of detection for ca-125 in human serum , and cervical and vaginal secretions was determined to be 0.50 u / ml . the precision and accuracy were within 12% in terms of coefficients of variation ( cvs ) for the low and high controls ( 35 and endometrial ca-125 was detected by immunohistochemical technique ( elivision plus ) using a commercially available kit ( maixin bio , fuzhou , china ) . four-m unstained slides were prepared from each case for immunohistochemical staining for anti - ca125 antigens with clone ov 125 diluted 1:2 . immunohistochemistry was performed by deparaffinization of slides in xylene , absolute ethyl alcohol , and degradated alcohols 96% and 70% . immunoperoxidase stains were performed using a modified labeled streptavidin technique and run on an automated system using a commercially available chromogen . the percentage of tissue area stained in 1012 high power fields and its intensity scored as 0 , 1 , 2 , and 3 . cancer tissue with staining of more than 50% of the area examined and an intensity of 2 and 3 was considered as positive ( score 1 ) . pathologic grading of the tumor cells was done according to the 1988 figo grading system . the tumor was graded based on the percentage of solid non - squamous growth as follows : grade 1 , 5% solid growth ; grade 2 , 650% solid growth ; grade 3 , > 50% solid growth . the overall grade of architecturally grade 1 or grade 2 tumors was increased by one if there was notable nuclear atypia . differences among groups of subjects were compared by the  or fisher s exact test . correlation analysis was performed to determine the relationship between the ca-125 levels measured in different biological matrices . a p value of < 0.05 was considered significant . in proliferative and secretory phases of healthy chinese women , the ca-125 contents in cervical and vaginal secretions were 483.56 , 114.79 , and 500.65 and 124.00 u / ml , respectively ( table 1 ) . the content of ca-125 in the serum was 6.8- and 28.8-fold lower than those in the vaginal and cervical secretions , respectively . there was insignificant difference in levels of ca-125 in serum , and cervical and vaginal secretions between the proliferative and secretory phase . in normal proliferative and secretory phases of menstrual cycle , most chinese women expressed endometrial ca-125 ( score 1 ) , but none of them expressed ca-125 at levels of score 2 or 3 . a correlation analysis indicated that there was a significant correlation between ca-125 levels in the serum and cervical and vaginal secretions in the proliferative phase ( p=0.004 and 0.003 , respectively ) , but there was no correlation between ca-125 levels in cervical and vaginal secretions . however , there was a correlation between ca-125 levels in cervical and vaginal secretions in the secretory phase ( p=0.0007 ) , while the correlation between serum ca-125 levels and cervical and vaginal secretions disappeared . in chinese women with non - functional polyps , the levels of ca-125 in serum , and cervical and vaginal secretions were slightly higher than those in healthy women , but did not achieve statistical significance ( table 1 ) . in 24 chinese women with non - functional polyps , 16 and 6 expressed ca-125 to score 2 and 3 , respectively ( table 2 ) . there was a significant difference in endometrial ca-125 expression level between non - functional endometrial polyps and normal endometrium ( =46.492 , p<0.0001 , see table 3 ) . in non - functional polyps , there were significant correlations between serum ca-125 levels and cervical and vaginal secretions ( p<0.05 ) . in addition , the levels of ca-125 in cervical secretions correlated with that in vaginal secretion . the expression profile of ca-125 in serum , and cervical and vaginal secretions in women with simple hyperplasia was similar to that in healthy women ( table 1 ) . however , the contents of ca-125 in serum , and cervical and vaginal secretions from women with complex hyperplasia were significantly higher than the corresponding values in healthy women or women with simple hyperplasia ( p<0.05 ) . in simple hyperplasia , there were significant correlations between serum ca-125 levels and cervical and vaginal secretions ( p<0.05 ) . in addition , the levels of ca-125 in cervical secretions correlated with that in vaginal secretion . in complex hyperplasia , there were significant correlations between serum ca-125 levels and cervical secretion ( p=0.016 ) , but not with vaginal secretion ( p=0.169 ) . in addition , the levels of ca-125 in cervical secretions significantly correlated with that in vaginal secretion ( p=0.0006 ) . the endometrial expression of ca-125 in 24 cases of simple hyperplasia was comparable to that of normal proliferative or secretory phase endometrium ( p=0.4354 by fisher s exact test ) . however , 16 and 10 out of 26 cases of complex hyperplasia showed score 2 and 3 endometrial staining of ca-125 , respectively . there was a significant difference in endometrial ca-125 expression levels between complex endometrial hyperplasia and simple hyperplasia or normal endometrium ( =37.182 , p<0.0001 ; =57.212 , p<0.001 , respectively ) . there was a significant difference in endometrial ca-125 expression levels between simple endometrial hyperplasia and polyps ( =27.932 , p<0.0001 ) , but there was no significant difference between in endometrial ca-125 expression levels between complex endometrial hyperplasia and polyps ( =2.925 , p=0.2317 ) , in 26 chinese women with confirmed endometrial cancer , grade 1 and 2 cancer had significantly higher ca-125 levels in serum , cervical and vaginal secretions compared to healthy women and women with simple hyperplasia ( table 1 ) . grade 1 and 2 endometrial cancer demonstrated an expression profile of ca-125 in serum , and cervical and vaginal secretions similar to that of complex hyperplasia . grade 3 endometrial cancer showed slightly higher levels of ca-125 than healthy women and women with simple hyperplasia , but significantly lower levels of ca-125 compared to grade 1 and 2 cancer . when all cases of endometrial cancer were pooled , there were significant correlations between serum ca-125 levels and cervical and vaginal secretions ( p<0.05 ) . in addition , the levels of ca-125 in cervical secretions correlated with that in vaginal secretion . however , when the patients were grouped based on pathological grade , such correlations disappeared . in addition , there was no significant correlation between serum ca-125 levels and endometrial expression of ca-125 . in 123 cases of endometrial cancer , 63 , 42 and 18 were pathological grade 1 , 2 , and 3 , respectively ( table 2 ) . overall , in 63 cases of grade 1 endometrial cancer , 33 and 30 showed score 2 and 3 staining of ca-125 , respectively ( figure 1 ) . this figure was 14 and 28 in 42 cases of grade 2 endometrial cancer . in 18 cases of grade 3 endometrial carcinoma , 16 and 2 displayed score 2 and 3 staining of ca-125 , respectively . overall , 63 ( 51.22% ) and 60 ( 48.78% ) subjects of 123 cases showed score 2 and 3 staining of endometrial ca-125 , respectively . there was a significant difference in endometrial ca-125 expression among patients with pathological grade 1 , 2 and 3 of endometrial carcinoma ( =15.632 , p=0.0004 ) . the endometrial expression of ca-125 in each grade of cancer was significantly different from that of normal endometrium . there was a significant difference in ca-125 expression between grade 1 and 3 endometrial carcinoma ( p=0.0058 by fisher s exact test ) whereas there was no significant difference in ca-125 expression between grade 1 and 2 endometrial carcinoma ( p=0.0717 by fisher s exact test ) . in addition , there was a significant difference in ca-125 expression between grade 2 and 3 endometrial carcinoma ( p=0.0001 by fisher s exact test ) . we further compared the difference in endometrial expression of ca-125 between endometrial cancer , polyps and hyperplasia and the results are listed in table 3 . there was a significant difference in endometrial ca-125 expression between cancer and polyps ( =29.646 ; p<0.0001 ) . there was a significant difference in endometrial ca-125 expression levels between grade 1 and 2 cancer and polyps ( =8.029 , p=0.0181 ; =12.382 , p=0.002 , respectively ) , but the difference between grade 2 cancer and polyps was insignificant ( =3.208 ; p=0.2011 ) . there was a significant difference in endometrial ca-125 expression between cancer and simple hyperplasia ( =137.66 ; p<0.0001 ) . there was a significant difference in endometrial ca-125 expression levels between grade 1 , 2 , or 3 cancer and simple hyperplasia ( =69.142 , p<0.0001 ; =52.562 , p<0.0001 ; =28.932 , p<0.001 , respectively ) . there was a significant difference in endometrial ca-125 expression between cancer and complex hyperplasia ( =16.603 ; p=0.0009 ) . there was a significant difference in endometrial ca-125 expression levels between grade 2 cancer and complex hyperplasia ( p=0.027 by fisher s exact test ) . however , there was no significant difference in endometrial ca-125 expression levels between grade 1 or 3 cancer and complex hyperplasia ( p=0.4878 and 0.0833 by fisher s exact test , respectively ) . in proliferative and secretory phases of healthy chinese women , the ca-125 contents in cervical and vaginal secretions were 483.56 , 114.79 , and 500.65 and 124.00 u / ml , respectively ( table 1 ) . the content of ca-125 in the serum was 6.8- and 28.8-fold lower than those in the vaginal and cervical secretions , respectively . there was insignificant difference in levels of ca-125 in serum , and cervical and vaginal secretions between the proliferative and secretory phase . in normal proliferative and secretory phases of menstrual cycle , most chinese women expressed endometrial ca-125 ( score 1 ) , but none of them expressed ca-125 at levels of score 2 or 3 . a correlation analysis indicated that there was a significant correlation between ca-125 levels in the serum and cervical and vaginal secretions in the proliferative phase ( p=0.004 and 0.003 , respectively ) , but there was no correlation between ca-125 levels in cervical and vaginal secretions . however , there was a correlation between ca-125 levels in cervical and vaginal secretions in the secretory phase ( p=0.0007 ) , while the correlation between serum ca-125 levels and cervical and vaginal secretions disappeared . in chinese women with non - functional polyps , the levels of ca-125 in serum , and cervical and vaginal secretions were slightly higher than those in healthy women , but did not achieve statistical significance ( table 1 ) . in 24 chinese women with non - functional polyps , 16 and 6 expressed ca-125 to score 2 and 3 , respectively ( table 2 ) . there was a significant difference in endometrial ca-125 expression level between non - functional endometrial polyps and normal endometrium ( =46.492 , p<0.0001 , see table 3 ) . in non - functional polyps , there were significant correlations between serum ca-125 levels and cervical and vaginal secretions ( p<0.05 ) . in addition , the levels of ca-125 in cervical secretions correlated with that in vaginal secretion . the expression profile of ca-125 in serum , and cervical and vaginal secretions in women with simple hyperplasia was similar to that in healthy women ( table 1 ) . however , the contents of ca-125 in serum , and cervical and vaginal secretions from women with complex hyperplasia were significantly higher than the corresponding values in healthy women or women with simple hyperplasia ( p<0.05 ) . in simple hyperplasia , there were significant correlations between serum ca-125 levels and cervical and vaginal secretions ( p<0.05 ) . in addition , the levels of ca-125 in cervical secretions correlated with that in vaginal secretion . in complex hyperplasia , there were significant correlations between serum ca-125 levels and cervical secretion ( p=0.016 ) , but not with vaginal secretion ( p=0.169 ) . in addition , the levels of ca-125 in cervical secretions significantly correlated with that in vaginal secretion ( p=0.0006 ) . the endometrial expression of ca-125 in 24 cases of simple hyperplasia was comparable to that of normal proliferative or secretory phase endometrium ( p=0.4354 by fisher s exact test ) . however , 16 and 10 out of 26 cases of complex hyperplasia showed score 2 and 3 endometrial staining of ca-125 , respectively . there was a significant difference in endometrial ca-125 expression levels between complex endometrial hyperplasia and simple hyperplasia or normal endometrium ( =37.182 , p<0.0001 ; =57.212 , p<0.001 , respectively ) . there was a significant difference in endometrial ca-125 expression levels between simple endometrial hyperplasia and polyps ( =27.932 , p<0.0001 ) , but there was no significant difference between in endometrial ca-125 expression levels between complex endometrial hyperplasia and polyps ( =2.925 , p=0.2317 ) , in 26 chinese women with confirmed endometrial cancer , grade 1 and 2 cancer had significantly higher ca-125 levels in serum , cervical and vaginal secretions compared to healthy women and women with simple hyperplasia ( table 1 ) . grade 1 and 2 endometrial cancer demonstrated an expression profile of ca-125 in serum , and cervical and vaginal secretions similar to that of complex hyperplasia . grade 3 endometrial cancer showed slightly higher levels of ca-125 than healthy women and women with simple hyperplasia , but significantly lower levels of ca-125 compared to grade 1 and 2 cancer . when all cases of endometrial cancer were pooled , there were significant correlations between serum ca-125 levels and cervical and vaginal secretions ( p<0.05 ) . in addition , the levels of ca-125 in cervical secretions correlated with that in vaginal secretion . however , when the patients were grouped based on pathological grade , such correlations disappeared . in addition , there was no significant correlation between serum ca-125 levels and endometrial expression of ca-125 . in 123 cases of endometrial cancer , 63 , 42 and 18 were pathological grade 1 , 2 , and 3 , respectively ( table 2 ) . overall , in 63 cases of grade 1 endometrial cancer , 33 and 30 showed score 2 and 3 staining of ca-125 , respectively ( figure 1 ) . this figure was 14 and 28 in 42 cases of grade 2 endometrial cancer . in 18 cases of grade 3 endometrial carcinoma , 16 and 2 displayed score 2 and 3 staining of ca-125 , respectively . overall , 63 ( 51.22% ) and 60 ( 48.78% ) subjects of 123 cases showed score 2 and 3 staining of endometrial ca-125 , respectively . there was a significant difference in endometrial ca-125 expression among patients with pathological grade 1 , 2 and 3 of endometrial carcinoma ( =15.632 , p=0.0004 ) . the endometrial expression of ca-125 in each grade of cancer was significantly different from that of normal endometrium . there was a significant difference in ca-125 expression between grade 1 and 3 endometrial carcinoma ( p=0.0058 by fisher s exact test ) whereas there was no significant difference in ca-125 expression between grade 1 and 2 endometrial carcinoma ( p=0.0717 by fisher s exact test ) . in addition , there was a significant difference in ca-125 expression between grade 2 and 3 endometrial carcinoma ( p=0.0001 by fisher s exact test ) . we further compared the difference in endometrial expression of ca-125 between endometrial cancer , polyps and hyperplasia and the results are listed in table 3 . there was a significant difference in endometrial ca-125 expression between cancer and polyps ( =29.646 ; p<0.0001 ) . there was a significant difference in endometrial ca-125 expression levels between grade 1 and 2 cancer and polyps ( =8.029 , p=0.0181 ; =12.382 , p=0.002 , respectively ) , but the difference between grade 2 cancer and polyps was insignificant ( =3.208 ; p=0.2011 ) . there was a significant difference in endometrial ca-125 expression between cancer and simple hyperplasia ( =137.66 ; p<0.0001 ) . there was a significant difference in endometrial ca-125 expression levels between grade 1 , 2 , or 3 cancer and simple hyperplasia ( =69.142 , p<0.0001 ; =52.562 , p<0.0001 ; =28.932 , p<0.001 , respectively ) . there was a significant difference in endometrial ca-125 expression between cancer and complex hyperplasia ( =16.603 ; p=0.0009 ) . there was a significant difference in endometrial ca-125 expression levels between grade 2 cancer and complex hyperplasia ( p=0.027 by fisher s exact test ) . however , there was no significant difference in endometrial ca-125 expression levels between grade 1 or 3 cancer and complex hyperplasia ( p=0.4878 and 0.0833 by fisher s exact test , respectively ) . a sensitive immunoradiometric assay for ca-125 was developed in 1983 , and several second - generation immunochemical methods are now available for accurate determination of this important tumor marker . to improve on the sensitivity and specificity of the first - generation assays , a double - determinant monoclonal antibody - based format was developed using 2 monoclonal antibodies with specificities against the antigenic domains oc125 and m11 in the large ca-125 protein . presently , serum ca-125 is widely used as a biochemical marker for the diagnosis of epithelial ovarian cancer , which is the fifth most common cancer of women in the united states . however , the assay for serum ca-125 is not useful for screening for ovarian cancer in asymptomatic women . serum ca-125 concentrations exceed 35 u / ml in 80% of patients with nonmucinous epithelial ovarian cancer , and the concentrations correlate well with the progression or regression of ovarian cancer [ 6,915 ] . we have found that cervical secretion contained 4.0-fold higher ca-125 than vaginal secretion in healthy women and the content of ca-125 in the serum was 6.8- to 28.8-fold lower than those in the vaginal and cervical secretions . it appears that cervical and vaginal secretions are better matrix than the serum for the monitoring of ca-125 content . epithelial cells in the cervix may produce more ca-125 than those in the vagina . since ca-125 is synthesized in epithelial cells of mllerian duct origin and then leaked into the circulation and secretions in the genital duct , it is not a surprise that the levels of ca-125 in the serum and cervical and vaginal secretions correlate , as observed in this study . positive staining for ca-125 is known to be present in normal endometrial tissue and especially during the secretory phase . consistent with this is our observation of weak staining of ca-125 in normal proliferative and secretory phase endometrium . slightly more cells in secretory phase endometrium were stained positively compared to proliferative phase endometrium . non - functional endometrial polyps are not considered to be precancerous lesions but a recent meta - analysis indicates that both symptomatic vaginal bleeding and postmenopausal status in women with endometrial polyps are associated with an increased risk of endometrial malignancy . multiple molecular mechanisms have been proposed to play a role in the development of endometrial polyps . these include monoclonal endometrial hyperplasia , overexpression of endometrial aromatase , and gene mutations . in this study , we can not find significantly increased ca-125 levels in the serum and cervical and vaginal secretions , but found that 66.67% and 25.00% of the subjects with polyps showed score 2 and 3 endometrial staining of ca-125 . this reflects that the muc16 gene has been significantly up - regulated in endometrial polyps . the widely used world health organization system classifies endometrial hyperplasia into four levels according to glandular crowing and nuclear appearance : simple , complex , simple atypical , and complex atypical hyperplasia . simple hyperplasia refers to diffuse and variably sized glands with a normal ratio of glands to stroma ; complex hyperplasia consists of architecturally irregular glands and an increased gland - to - stroma ratio . when there is nuclear enlargement with chromatin evenly dispersed or clumped , it is called simple or complex atypical hyperplasia . in this study , simple hyperplasia did not show significantly elevated ca-125 in the serum and cervical and vaginal secretions and endometrial expression of ca-125 , while complex hyperplasia displayed significantly increased ca-125 in the serum and cervical and vaginal secretions and endometrial expression of ca-125 . as such , ca-125 in the serum , cervical and vaginal secretions , and endometrium long - term risk among women with simple or complex hyperplasia is less than 5% , but the risk among women with atypical hyperplasia is about 30% . the results showed that there was a significant difference in endometrial ca-125 levels between normal subjects and patients with complex hyperplasia . this implicates that endometrial ca-125 expression determination may be used as a screening approach to identifying high - risk subpopulation with a potential to progress to carcinoma . with a lifetime risk of 23% among women approximately 7580% of ec cases have the international federation of gynecology and obstetrics ( figo ) stages i  ii disease confined to the uterine corpus due to early symptoms including vaginal bleeding . the most common basis for determining the risk of recurrent disease has been classification of endometrial cancers into two subtypes based on light microscopic appearance , clinical behavior , and epidemiology . type i ec accounts for the majority ( 7080% ) of cases and is associated with unopposed estrogen exposure and are often preceded by premalignant disease ( e.g. endometrial hyperplasia ) . type i is associated with a low - stage , low - grade , endometrioid histology , while type ii is characterized by a high - stage , high - grade and non - endometrioid histology ( usually papillary serous or clear cell ) . hormonal risk factors have not been identified and there is no observed premalignant phase for type ii ec . type i occurs predominantly in pre- and perimenopausal women but type ii usually occurs 510 years later than type i cancer . type i often has a good prognosis whereas type ii is associated with a poor prognosis due to a high frequency of distinct spread to pelvic lymph nodes . the morphological and clinical differences are paralleled by remarkable distinct genetic mutations in that type i and type ii carry mutations of independent sets of genes . type i ec has defects in dna - mismatch repair with microsatellite instability observed in 2045% patients , and mutations in pten , k - ras , pik3ca , and -catenin encoded by ctnnb1 genes , and type ii shows aneuploidy and p53 , her2/neu , p16 and e - cadherin mutations . although most ec patients are cured by surgery alone , about 1520% with no signs of locally advanced or metastatic disease at primary treatment recurs , with limited responsiveness to systemic therapy . our study has demonstrated that endometrial cancer had a significantly increased ca-125 in the serum and cervical and vaginal secretions . the increase of ca-125 content in serum , cervical and vaginal secretions was lesser significant in grade 3 cancer than that in grade 1 and 2 cancer . it appears that ca-125 synthesized by tumor cells is prevented from entry into the blood circulation in grade 3 cancer due to the presence of a membrane barrier . our study showed that endometrial ca-125 expression was significantly elevated in endometrial cancer compared to normal endometrium or endometrium with simple hyperplasia , with the tissue from all ec cases expressing ca-125 . 47.62% and 66.67% of pathological grade 1 and 2 endometrial cancer expressed a score 3 staining of ca-125 , but only 11.11% grade 3 endometrial cancer showed a score 3 staining of ca-125 . grade 3 endometrial cancer may express less ca-125 due to reduced production of this tumor antigen and/or increased degradation . compared to low - grade ecs ( grade 1 and 2 ) , grade 3 ecs show a lower frequency of expression of estrogen receptor and progesterone receptor , with a higher frequency of expression of p16 , p53 and insulin - like growth factor 2 mrna - binding protein 3 ( imp3 ) . ca-125 may be used in combination with these immunomarkers to distinguish between low grade ( grade 1 and 2 ) and high grade ( grade 3 ) ecs . notably , when all cases of endometrial cancer were pooled , there were significant correlations between serum ca-125 levels and cervical and vaginal secretions . however , there was no significant correlation between serum ca-125 contents and endometrial expression levels of ca-125 in our study , probably due to the presence of a barrier that blocks the entry of ca-125 from tumor cells into the circulation . in summary , there was a relatively high content of ca-125 in cervical and vaginal secretion but only a weak ca-125 expression in normal endometrium and simple endometrium hyperplasia . the levels of ca-125 in serum , and cervical and vaginal secretions were significantly increased in complex hyperplasia and endometrial cancer , but not in polyps and simple hyperplasia . there were significantly increased endometrial ca-125 expression in endometrial polyps , complex hyperplasia , and endometrial carcinoma . these findings indicate that endometrial ca-125 expression together with its levels in the serum and cervical and vaginal secretions can be used as a potential biomarker in the diagnosis of precancerous diseases and endometrial carcinoma in chinese women . further large - scale and long - term studies are required to evaluate the role of serum , cervical and vaginal secretions and tissue ca-125 levels in the diagnosis and prognosis prediction of endometrial cancer .
summarybackgroundserum ca-125 has been used as a biomarker of gynecological tumors . in this study , we investigated the ca-125 levels in cervical and vaginal secretions from chinese patients with endometrial polyps , hyperplasia and carcinoma in comparison with those in endometrium and serum.material/methodsan electro - chemiluminescent immunoassay was utilized to determine the levels of ca-125 in 51 healthy chinese women and 97 patients with polyps , hyperplasia or endometrial cancer . 
 an immunohistochemistry method was used to detect endometrial ca-125 expression in 242 subjects.resultsour study demonstrated that serum ca-125 levels were much lower than those in cervical and vaginal secretions in healthy and diseased women . 
 the levels of ca-125 in serum , and cervical and vaginal secretions were significantly increased in complex hyperplasia and endometrial cancer . 
 the increase of ca-125 content in serum , cervical and vaginal secretions was lesser significant in grade 3 cancer than that in grade 1 and 2 cancer . 
 generally , serum ca-125 levels correlated with those in cervical and vaginal secretions and ca-125 content in cervical secretion correlated with that in vaginal secretion . 
 there was only a weak ca-125 expression in normal endometrium and simple endometrial hyperplasia . 
 there was a significant difference in ca-125 expression among patients with pathological grade 1 , 2 and 3 of endometrial carcinoma.conclusionsendometrial ca-125 expression together with its levels in the serum and cervical and vaginal secretions can be used as a potential biomarker in the diagnosis of precancerous diseases and endometrial carcinoma