The Clinical Diagnostic Value Of Combined Determination Of Serum And Urinary Mesothelin Together With Serum CA125 For Epithelial Ovarian Cancer

Backgroud and purpose90% of ovarian cancers are epithelial ovarian cancer (hereinafter referred to as ovarian cancer). early onset is concealed, early detection is difficult,disseminates and transfers quickly and treatment is intractable, so it is the ledading cause of death in gynecological malignancies. Recent studies have shown that incidence rate of ovarian cancer is on the rise, which is a serious threat to women's health.90% of early stage ovarian cancer patients can be cured with currently available therapy.Unfortunately, only 15% to 20% of patients with advanced stage ovarian cancer will be cured, despite the continuous improvement of surgical treatment and chemotherapy. At present, only 25% of ovarian cancers are detected as early stage. So that more patients with ovarian cancer were diagnosed at an early stage is important in improving overall survival. So do a good job screening for ovarian cancer, look for tumor markers with high sensitivity and specificity, and improve the early diagnosis of ovarian cancer,which is important to further improving the treatment outcome ,reducing mortality in patients with ovarian cancer and improving 5-year survival rate. A lot of researches have done to look for the ovarian cancer marker in the serum at home and abroad,but a few tests make efforts to look for the ovarian cancer markers in urine. Mesothelin is a cell surface protein, studies show that: mesothelin expression in normal tissues is strictly limited, exists only in the mesothelial organization.but in a variety of tumor tissues, such as mesothelioma, pancreatic cancer, non-small-cell carcinoma and ovarian cancer mesothelin expression is high-level, and studies also show that high expression of mesothelin are found in ovarian cancer patients serum and urine. CA125 is a mucin glycoprotein, CA125 level in serum has been widely used in clinical diagnosis and monitoring of ovarian cancer at home and abroad. This test uses enzyme-linked immunosorbent assay (ELISA) to detect mesothelin levels of serum and urine in epithelial ovarian cancer patients, and to investigate the clinical value of mesothelin as a marker for epithelial ovarian cancer.Materials and Methods1 Experimental samples:We detected 73 epithlial ovarian tumor with pathology diagnosis in the First Affiliated Hospital of Zhengzhou Unviersity during February 2008 to March 2009,which was divided into two groups by pathology.one group have 41 ovarian epithelial cancers, (34.6±8.2) years old (12 cases of the stagesⅠ～Ⅱperiod,29 cases of the stagesⅢ～Ⅳperiod,27 cases of the serous carcinoma, 14 cases of the Mucinous carcinoma). The other group have 32 benign ovarian tumor, (33.7±6.1)years old(19 cases of the serous cystadenoma,13 cases of the Mucinous cystadenoma).30 healthy women which were randomly selected was control group, (35.4±7.5) years old. Three groups have no significant difference in age and have no history of other cancers.We phlebotomize 5ml fasting blood from patients (specimens before radiation and chemotherapy or other treatment), all of the blood specimen were saved in clean tubes coagulated for 30min in room temperature, and then centrifugalized in 4 degrees Celsius,3000r/min, for 5min.We got upper serum into EP tube freeze-stored in-70°c refrigerator. We acquired 10ml fasting urine and then got upper urine into EP tube freeze-stored in-70°c refrigerator after 5min centrifugalized. It is the same to the controls. 2 Test methods:We determined the mesothelin and CA125 serum levels and mesothelin urine levels by enzyme-linked immunosorbent assay (ELISA). Fluctuation alert was got from normal healthy women (x±1.96s), after calculation upper threshold of urine is 2.7ng/mL, upper threshold of serum is 4.6ng / mL.. Serum CA125 take more than 35U/ml positive.3 Statistical analysis:The SPSS statistical package program 13.0 was used. Comparison between the two groups with t-test, counted datas were usedχ2 test the rate of usingχ2 test analysis. a=0.05 were deemed significant.Results1 Mesothelin levels in serum and urine of ovarian cancer patients respectively were (15.07±1.50)ng/ml, (10.21±1.01)ng/ml, mesothelin levels in serum and urine of ovarian benign tumor patients respectively were (4.56±0.59)ng/ml, (3.43±0.38)ng/ml; mesothelin levels in serum and urine of control group were (3.58±0.53)ng/ml, (2.02±0.32)ng/ml. Three groups have significant difference in mesothelin level (p<0.001).There was no significant difference between patients with ovarian benign tumor and control group (p>0.05). Serum CA125 was (649.23±211.37)U/ml in ovarian cancer group, sreum CA125 was (42.62±9.29)U/ml in ovarian benign tumor group, serum CA125 was (21.25±6.69)U/ml in normal control group. Three groups have significant difference in serum CA125 (p<0.05). There was no significant difference between Patients with ovarian benign tumor and control group (p>0.05).2 The sreum and urine mesothelin levels of early-stage ovarian cancer (ⅠⅡ)were (8.21±2.41)ng/ml,(6.92±1.84)ng/ml, and that of advanced-stage(Ⅲ-Ⅳ) were (18.07±1.76)ng/ml,(13.21±1.02)ng/ml,and the difference was significant (p<0.05);the serum and urine mesothelin levels in patients with ovarian serous cystadenocarcinoma were (16.18±1.05)ng/ml,(11.23±1.16)ng/ml,and that of ovarian mucinous cystadenocarcinoma were (13.57±1.47)ng/ml,(9.42±1.21)ng/ml,and the difference was not statistically significant.(p>0.05).3 The mesothelin positive rate of serum and urine sensitivity were up to 33.3% and 50% in early-stage ovarian cancer,which were up to 69.9% and 75.9% in advanced-stage,all the difference have statistics significance (p<0.05).The mesothelin positive rate in ovarian serous cystadenocarcinoma were up to59.3% and 70.4% which were up to 57.1% and 65.9% in ovarian mucinous cystadenocarcinoma, all with the difference non-statistics significance(p>0.05). The sensitivity of serum CA125 diagnosis was up to 50.0% in early-stage ovarian cancer, and that of advanced-stage was up to 86.2%, the difference have statistics significance (p<0.05),and the difference have statistics significance (p<0.05)between the ovarian serous cystadenocarcinoma and ovarian mucinous cystadenocarcinoma.4 The sensitivity and accuracy of serum mesothelin diagnosis were up to 58.5% and 83.9%;The sensitivity and accuracy of urinary mesothelin diagnosis were up to 68.3% and 95.3%;The sensitivity and accuracy of serum CA125 diagnosis were up to 75.6% and 66.1%. Combination of serum mesothelin and urinary mesothelin and CA125, the sensitivity and accuracy were up to 95.1%,96.8%.Conclusion1 The combination of serum mesothelin and urinary mesothelin and CA125 have relatively high sensitivity and accuracy in diagnosis of ovarian cancer,which improve the accuracy of the diagnosis ovarian cancer to a large extent. so they have important value, might be used as epithelial ovarian cancer tumor marker.2 Combining the urine mesothelin of early stage and advanced stage ovarian cancer,the positives rates were closed to each other,Which shows urine mesothelin can serve as an indicator for early ovarian cancer.