Evaluation of CA125 as a circulating tumor marker for ovarian cancer

CA125 usefulness was evaluated using sera from healthy persons, pregnant women, and patients with ovarian and other tumors. Since serum CA125 levels significantly depended on sex and age in healthy persons, the original cut-off levels were 40 and 25 U/ml in terms of sex and age. Changes in CA125 levels within 40 U/ml were observed during the menstruation cycle. Elevation of CA125 levels was also observed during the first trimester of pregnancy, but these levels fell below 50 U/ml as pregnancy progressed. Immunostaining of the endometrium with OC125 suggested that ovarian function may play an important role in production of CA125 in early pregnancy and menstruating young women. Elevated levels of CA125 were detected in 33/34 (97%) cases with surgically demonstrated ovarian cancer. The clinical usefulness of CA125 for monitoring the course of ovarian cancer was reconfirmed. Practical application of CA125 proved to be useful for the early detection of ovarian cancer and confirmation of the complete disappearance of any tumor.     

Estimation of the usefulness of neoplastic markers TPS and CA 125 in diagnosis and monitoring of ovarian cancer.

PURPOSE: We have undertaken an attempt to compare the suitability of tumor markers TPS (tissue polypeptide specific antigen) and CA125 for diagnosis and monitoring of ovarian cancer patients. METHODS AND MATERIAL: The studies were performed on 33 patients treated for ovarian cancer in the Department of Oncology, Karol Marcinkowski School of Medicine, Poznań from 1995-1996, Serum levels of TPS and CA125 were determined before surgery and at each chemotherapy course. CONCLUSION: Estimation of the neoplastic markers TPS and CA125 is suitable for diagnosis of ovarian cancer. Parallel use of TPS and CA125 in ovarian cancer patients increases sensitivity of the diagnosis. Estimation of TPS is highly suitable and estimation of CA125 is of low value in detection of mucinous ovarian cancer. Serum levels of the neoplastic markers TPS and CA125 decrease after total or debulking surgery for ovarian cancer. Serum TPS and CA125 levels reflect the course of the neoplastic process during chemotherapy.     

CA125 in ovarian cancer: European Group on Tumor Markers guidelines for clinical use

CA125 is currently the most widely used tumor marker for ovarian epithelial cancer. The aim of this article is to provide guidelines for the routine clinical use of CA125 in patients with ovarian cancer. Due to lack of sensitivity for stage I disease and lack of specificity, CA125 is of little value in the detection of early ovarian cancer. At present, therefore, CA125, either alone or in combination with other modalities, cannot be recommended for screening for ovarian cancer in asymptomatic women outside the context of a randomized controlled trial. Preoperative levels in postmenopausal women, however, may aid the differentiation of benign and malignant pelvic masses. Serial levels during chemotherapy for ovarian cancer are useful for assessing response to treatment. Although serial monitoring following initial chemotherapy can lead to the early detection of recurrent disease, the clinical value of this lead-time is unclear. CA125 is the ovarian cancer marker against which new markers for this malignancy should be judged.     

Preoperative plasma osteopontin level as a biomarker complementary to carbohydrate antigen 125 in predicting ovarian cancer

AIM: New biomarkers other than carbohydrate antigen (CA) 125 are needed for the detection of ovarian cancer. Osteopontin (OPN) is one of the candidates identified by high-throughput complementary DNA microarray techniques. We evaluated the preoperative plasma OPN level as a diagnostic biomarker for ovarian cancer in comparison with CA125. METHODS: Preoperative plasma OPN and CA125 levels were measured and compared in 32 patients with ovarian cancer, 34 patients with benign ovarian tumor, 30 patients with other gynecologic cancers and 31 healthy women. Preoperative plasma OPN levels were also assessed according to tumor stage, the volume of ascites and histological types. The sensitivity and specificity for predicting ovarian cancer was compared between OPN and CA125. RESULTS: Preoperative plasma OPN levels were significantly higher in patients with ovarian cancer than in those with benign ovarian tumor, in other gynecologic patients or in healthy women. Stage IV ovarian cancer patients and ovarian cancer patients with ascites had higher plasma OPN levels than those without ascites and in a lower stage. There was no relation between OPN and the histological type. The sensitivity of preoperative plasma OPN in detecting ovarian cancer was 81.3% and almost reached that of CA125. The specificity was moderate. Sensitivity increased to 93.8% with the combination of CA125, compared to 84.4% with CA125 alone. CONCLUSION: Preoperative OPN is a useful biomarker for predicting ovarian cancer. It is especially useful when used complementary to CA125. Larger studies of patients with ovarian cancer showing a low CA125 level or in early stages of ovarian cancer are needed.     

Prospective evaluation of serum CA 125 levels for early detection of ovarian cancer.

Detection of ovarian cancer at an early stage should reduce the mortality associated with this disease. Through the Stockholm Population Registry, 5550 apparently healthy women were enrolled in a study designed in part to define the use of the CA 125 radioimmunoassay (RIA) as an initial test for early detection of ovarian cancer. Women whose CA 125 levels were elevated and an equal number of age-matched controls with normal levels were followed by means of pelvic examinations, transabdominal sonography, and serial CA 125 determinations. Of the 175 women with high CA 125 levels, six were found to have ovarian cancer: two each in stages IA, IIB, and IIIC. Of those with normal-range CA 125 levels, three had ovarian cancer as identified through the Swedish Cancer Registry; all three were under 50 years of age. Ovarian cancer was diagnosed on laparotomy in six of the women age 50 or over. Using thresholds of 30 and 35 U/mL, the rates of specificity for the CA 125 RIA were 97 and 98.5%, respectively, for women age 50 or older, and 91 and 94.5%, respectively, for those younger than 50 years of age. Thus, the specificity of the CA 125 RIA is adequate in postmenopausal women to undertake a larger study to determine whether screening using CA 125 influences survival of patients with ovarian cancer.     

Evaluation of selected serum protein markers as early detectors of ovarian cancer

OBJECTIVE: an attempt to determine the value of the simultaneous quantization of osteopontin (OPN), insulin-growth factor II (IGF II), leptin, prolactin and CA 125 for early detection of ovarian cancer. MATERIALS AND METHODS: Prospective study of 69 women including: 15 females with ovarian cancer; 33 females with benign ovarian neoplasm; 21 disease-free females; The levels of IGF II, prolactin, leptin and CA 125 were determined in serum, while the level of OPN was checked in plasma. RESULTS: The concentrations of IGF II, leptin and prolactin do not let us distinguish among disease-free females, females with ovarian cancer and those with benign ovarian neoplasms on the basis of biochemical markers. The comparison of OPN and CA 125 levels showed significant differences in the concentrations of the biomarkers between disease-free females and females with ovarian cancer, as well as between females with benign ovarian neoplasms and females with ovarian cancer. The ROC curves for two groups: disease-free females and females with ovarian cancer, proved the diagnostic value of OPN and CA 125. CONCLUSIONS: The simultaneous quantization of OPN, IGF II leptin and prolactin has not been proved useful for the early detection of ovarian cancer. Statistically significant increase of OPN & CA 125 levels was noted in case of women with ovarian cancer diagnosed through microscopic examination. The analysis of ROC curves showed comparable diagnostic usefulness of both markers. Quantization of OPN may have an additional value for treatment monitoring of women diagnosed with ovarian cancer but with concentration of CA 125 within the reference value.     

CA125 expression at clinical diagnosis by ovarian carcinoma not detected through antecedent serum CA125 screening

At the time of clinical presentation with ovarian carcinoma, 85% of women have an elevated serum level of the CA125 antigen, but the duration of the preclinical phase of expression of CA125 is unknown. From the database of The Royal London Hospital ovarian cancer screening project, 19 women were identified who had a serum CA125 level <30 IU ml⁻¹, measured between 2 and 24 months prior to their clinical diagnosis of ovarian cancer. Histological sections of tumor removed from these women were reviewed. In 17 cases tumor tissue was immunocytochemically stained for CA125 expression. Tumor blocks of 40 women presenting clinically with ovarian cancer with known preoperative CA125 levels were also stained for CA125 expression. The serum CA125 level at the time of diagnosis was available in six of the 19 screening study cases, four of which had levels> 30 IU ml⁻¹. In five of the 13 cases with unknown serum CA125 levels, ovarian tumor tissue expressed CA125. Among the 40 controls, 24 tumors expressed CA125 and all 24 had a serum level greater than 47 IU ml⁻¹. An annual screening test using serum levels of CA125 at a cut-off of 30 IU ml⁻¹, cannot detect all cases of ovarian cancer that express the antigen at the time of clinical diagnosis. The development of a panel of complementary tumor markers will be necessary to provide a test with a higher sensitivity for the detection of preclinical ovarian cancer.     

Evaluation of HE4 as an extrabiomarker to CA125 to improve detection of ovarian carcinoma: is it time for a step forward?

Purpose

To evaluate human epididymis protein 4 (HE4) as an extrabiomarker to cancer antigen 125 (CA125) to improve the detection of ovarian carcinoma.

Methods

Sixty patients with ovarian carcinoma, 50 patients with benign ovarian tumors and 30 healthy women were included in the present study. Serum concentration of HE4 was assayed using ELISA technique, while CA125 was assayed using chemiluminescent enzyme immunoassay.

Results

The median CA125 and HE4 serum values were significantly higher among ovarian cancer patients when compared with healthy control However, the median serum levels of CA125 but not HE4 were significantly higher among patients with benign ovarian tumors as compared to healthy women. Based on the receiver operator characteristics curve analysis, HE4 had higher sensitivities than CA125 for the detection of ovarian cancer at 90, 95 and 98 % specificities and the combination of both markers yielded a higher sensitivity than either alone. However, CA125 but not HE4 had higher sensitivities for the detection of benign ovarian tumors at the same specificities. In addition, a positive correlation was observed between HE4 and CA125 among patients with ovarian carcinoma.

Conclusion

HE4 is a valuable marker for ovarian cancer diagnosis and when combined with CA125, they had a higher sensitivity at a set specificity, thus providing a more accurate predictor of ovarian cancer than either alone.     

间皮素与血清CA125联合检测上皮性卵巢癌的临床价值

目的研究间皮素(mesothelin)在上皮性卵巢癌血清及尿液中的表达水平,与血清CA125联合检测上皮性卵巢癌的临床应用价值。方法 2009年4月在郑州大学第一附属医院,采用ELISA法检测41例上皮性卵巢癌、32例卵巢良性肿瘤、30例正常人群血清及尿液间皮素水平和血清CA125水平。结果卵巢癌患者血清及尿液中间皮素水平明显高于卵巢良性肿瘤组和正常对照组,差异有统计学意义(P<0.01),血清及尿液间皮素水平在卵巢良性肿瘤组与正常对照组间差异均无统计学意义(P>0.05)。血清间皮素检测上皮性卵巢癌敏感度、特异度分别为58.5%、83.9%,联合血清CA125检测其敏感度、特异度分别为85.4%、85.5%;尿液间皮素检测上皮性卵巢癌的敏感度、特异度分别68.3%、93.5%,联合血清CA125检测其敏感度、特异度分别为92.7%、96.8%,联合血清间皮素、尿液间皮素和血清CA125检测其灵敏度和特异度为95.1%、96.8%。结论血清及尿液间皮素联合CA125检测将有助于卵巢癌的早期检测。     

联合检测血清及尿液中bcl-2与血清CA125水平对卵巢上皮性癌的诊断价值

目的:研究凋亡相关基因bcl-2在卵巢上皮性癌患者血清及尿液的表达水平,及其与血清CA125联合检测诊断卵巢上皮性癌的临床价值。方法:采用ELISA法检测50例卵巢上皮性癌、20例卵巢良性肿瘤、18例正常人血清及尿液bcl-2水平和血清CA125水平。结果:卵巢癌患者血清及尿液bcl-2水平明显高于卵巢良性肿瘤组和正常人群组,差异有统计学意义(P0.05)。血清bcl-2水平在卵巢良性肿瘤组与正常对照组之间无显著差异(P0.05),尿液bcl-2水平在卵巢良性肿瘤组与正常对照组之间差异有统计学意义(P0.05)。血清bcl-2检测诊断卵巢癌的敏感度、特异度分别为68%、84.21%,联合血清CA125检测其敏感度、特异度分别为86%、86.84%;尿液bcl-2检测的敏感度、特异度分别为76%、89.47%,联合血清CA125检测其敏感度、特异度分别为94%、94.74%。结论:联合检测血清及尿液bcl-2与血清CA125水平有助于卵巢癌的术前诊断。     

Tumor marker CA 125 in diagnosis, monitoring management and follow-up of patients with ovarian tumors.

The concentration of CA 125 was defined in the blood serum of 151 patients with ovarian tumors: benign--49, borderline--5 and malignant--97. In 75.7% of benign tumors CA 125 concentrations did not exceed the normal level. In two from five patients with borderline tumors CA 125 concentration varied from 47 to 130 U/ml. High levels of CA 125 (from 125 to 10.000 U/ml and higher) were revealed in 54 from 57 patients (94.7%) with malignant ovarian tumors. If in Stages I and II elevated CA 125 levels (from 125 to 430 U/ml) were discovered in 71.4% and 80.0% of the cases, respectively, then in Stages III and IV CA 125 levels rose from 300 to 10.000 U/ml and higher in all cases. High CA 125 concentrations were noticed in 95.7% of patients with clinical signs of recurrences of the disease, and it was proved at "second-look" surgery. Thus, it was expedient to use CA 125 widely for an early detection of ovarian cancer, as a control on the efficiency of therapy and in diagnosis of subclinical recurrences of the disease.     

Serum CA 125 in epithelial ovarian cancer. A longitudinal study

Plasma levels of CA 125 were determined in 113 patients with ovarian cancer of epithelial origin. Of these, 69 patients had CA 125 measured before the first laparotomy and 84.6% of them had a CA 125 level greater than 35 U/ml. In 87 of the 113 patients whose tumour was producing CA 125, a good correlation was observed between the CA 125 levels and the clinical follow-up: 95.7% of the patients in remission had levels less than 35 U/ml, whereas all the patients with no change or with a progressive disease had levels greater than 35 U/ml. Furthermore in recurrent disease the levels of CA 125 were also increased (greater than 35 U/ml) in 92.3% of the patients. Thus, CA 125 measurements at regular intervals are of great clinical value in following the evolution of a tumour or the success of a therapy, but unfortunately do not allow detection of an ovarian tumour at an early stage.     

Serum CA 125 in epithelial ovarian cancer. A longitudinal study

Summary. Plasma levels of CA 125 were determined in 113 patients with ovarian cancer of epithelial origin. Of these, 69 patients had CA 125 measured before the first laparotomy and 84.6% of them had a CA 125 level >35 U/ml. In 87 of the 113 patients whose tumour was producing CA 125, a good correlation was observed between the CA 125 levels and the clinical follow-up: 95.7% of the patients in remission had levels < 35 U/ml, whereas all the patients with no change or with a progressive disease had levels >35 U/ml. Furthermore in recurrent disease the levels of CA 125 were also increased (>35 U/ml) in 92.3% of the patients. Thus, CA 125 measurements at regular intervals are of great clinical value in following the evolution of a tumour or the success of a therapy, but unfortunately do not allow detection of an ovarian tumour at an early stage.     

Elevated serum levels of macrophage colony-stimulating factor and OVX1, 11 months prior to the diagnosis of stage IC ovarian cancer

In published trials, CA125 has been utilized to trigger ultrasound examination for the early detection of ovarian cancer. Although serum CA125 levels can be elevated prior to clinical detection of ovarian cancer, only approximately half of patients with stage I disease will have an abnormal value. A combination of CA125, macrophage colony-stimulating factor (M-CSF) and the mucin marker OVX1 will detect> 95% of stage I patients, but it is not known whether the markers can be elevated prior to clinical detection of the disease. A postmenopausal patient was found to have small unilocular bilateral cystic adnexal lesions during an abdominal ultrasound examination. No pelvic abnormality could be palpated. Serum levels of the CA125 antigen were within the normal range. Progressive ultrasound changes prompted a laparotomy II months later, and the diagnosis of a stage IC serous cystadenocarcinoma of the ovary was established. A retrospective analysis of stored serum samples revealed that this patient had elevated serum levels of M-CSF and OVX1 at the time of the original ultrasound scan. Interpreted within the context of a potential screening strategy for ovarian cancer, these data illustrate that either or both of these tumor markers and/or ultrasound could have identified this ovarian cancer many months prior to the actual diagnosis, while the disease was at an early stage.     

Prospective evaluation of serum CA 125 levels in a normal population, phase I: The specificities of single and serial determinations in testing for ovarian cancer

To determine the potential efficacy of the CA 125 assay as one component of a strategy for early detection of ovarian malignancy, serum CA 125 levels were determined in 1082 women 40 years of age or older in Stockholm. Initial serum CA 125 levels exceeded 35 U/ml in 36 women (3.3%) and 65 U/ml in 11 women (1.0%), placing the exact 95% upper confidence limits on false positive rates for a single screen at 4.3 and 1.7%, respectively. Follow-up CA 125 levels were obtained for those women with initially elevated levels and a group of age-matched controls. Mean CA 125 levels declined significantly for women with initially elevated levels (P = 0.0014). Interindividual variation and variation within individual subjects over the entire follow-up period were 52 and 35%, respectively. Of the 36 subjects with initially elevated serum CA 125 levels, only 2 showed a doubling of these levels; in only 1 of these 2 was this increase sustained. Intensive clinical follow-up with pelvic examination and ultrasonography, with investigators blinded to CA 125 results, led to the diagnosis of Stage III ovarian cancer in the latter individual. Diagnosis was made 21 months after the initially elevated serum CA 125 measurement and 15 months after the first measured doubling of that level. Because no other malignancies were identified at entry or during the follow-up period (median 560 days) in the women with elevated CA 125 levels, the specificity of the assay over that time period would have been 99.9% using the doubling of an initially elevated value as the criterion for determining positivity and 100% using as the criterion a sustained increase in level for those with initially elevated levels that doubled. These results support the continued investigation of longitudinally collected CA 125 levels to identify individuals at high risk for ovarian malignancy.     

The value of CA 125 determination in the serum of patients with ovarian cancer

The circulating ovarian cancer associated antigen CA 125 was determined in serum of 63 patients with ovarian malignancies by radioimmunometric solid phase assay using the monoclonal antibody OC 125 as catcher and tracer. The results of 41 patients with 43 active tumour situations were compared with the CA 125 serum levels of 27 patients without recurrence after therapy of ovarian cancer and 49 benign ovarian tumours. Significant differences exist between these three groups (p less than 0.001) with elevated values (greater than 35 U/ml) in 84 per cent in ovarian carcinoma, 22 per cent in benign tumours and nought per cent in woman without recurrence in follow-up. The pre-operative sensitivity in ovarian cancer is 93 per cent (in epithelial carcinoma 96 per cent) with a distinct dependence of the CA 125 serum levels on the stage of the disease (stage III and IV versus stage I and II; p less than 0.01). A positive correlation of CA 125 values to clinical status was found in 82 per cent in follow-up. Increasing values of CA 125 can detect the recurrence any months earlier than the clinical examination. Decreasing serum levels in chemotherapy don't reflect the objective tumour remission in every case. Because of elevated values in benign and inflammatory adnexal tumours and the relative low sensitivity in borderline cases (three of seven patients greater than 35 U/ml) the CA 125 assay seems not be suitable for a screening method. However it is a substantial amplification in control of therapeutic success and an early detection of recurrence of ovarian cancer disease.     

Serum CA 125, carcinoembryonic antigen, and CA 19-9 as tumor markers in borderline ovarian tumors

OBJECTIVES: The goals of this study were to analyze preoperative serum levels of CA 125, carcinoembryonic antigen (CEA), and CA 19-9 in patients with borderline ovarian tumors and to investigate if routine assessment of these markers in follow-up may lead to earlier detection of recurrence. METHODS: For patient identification a database was used, in which data from all patients treated for gynecologic malignancies in the Department of Gynecologic Oncology, University Hospital Groningen, The Netherlands, are compiled. Between 1982 and 1997, 44 patients with borderline ovarian tumors were identified. Clinical data and serum CA-125 and CEA levels were retrieved from the database. CA 19-9 levels were determined in retrospect in available stored preoperative (24 patients) and follow-up (43 patients) serum samples. RESULTS: Preoperative CA 125 levels were elevated in 8 of 33 (24%), CEA levels in 3 of 32 (9%), and CA 19-9 levels in 11 of 24 (46%) cases. In patients with mucinous tumors preoperative CA 19-9 was more frequently elevated (8/14, 57%) than CA 125 (3/20, 15%) (P = 0.02) or CEA (2/18, 11%) (P = 0.02). Complete follow-up serum CA 125, CEA, and CA 19-9 levels were available for 43 of 44 patients. Median follow-up was 84 months (range, 22-204). During follow-up two patients (5%) had recurrent disease. In one patient CA 125 became elevated at the time of recurrence; in the other patient (in retrospect) the CA 19-9 level did not return to normal after surgery, but kept rising, preceding clinical symptoms of recurrence for 13 months. CONCLUSIONS: If one chooses to use serum markers in follow-up of mucinous borderline ovarian tumors CA 19-9 should be included. Measurement of serum tumor markers in the follow-up of patients with borderline ovarian tumors may lead to earlier detection of recurrence in only a very small proportion of patients, while the clinical value of earlier detection of recurrence remains to be established.     

Predictive values of CA 125 antigen levels and CT scan in second-look procedures for ovarian cancer

23 patients with ovarian cancer were investigated 10 days after their last regimen of chemotherapy by CT scan and CA 125 in comparison with 'second-look' findings. In 17 out of 23 cases the CT scan results correlated with the operative ones. There were 6 false-negative findings but no false-positives. In all cases serum CA 125 levels correlated with the second-look operation. Our data suggest that the upper limit of CA 125, especially for patients, with negative findings, is less than or equal to 20 U/ml which is much lower than that of 35 U/ml, which is generally accepted. They also indicate the value of CA 125 in the detection of persistent ovarian cancer and the value of the CT scan in the detection of liver metastases. According to the above findings we question the value of the second-look operation in certain cases of ovarian cancer.     

CA 125 in the serum and tissue of patients with gynecological disease

Summary Serum levels of CA 125 were determined in 239 patients suffering from gynecological malignancies. The upper limit for normal was 35 U/ml. Raised levels were found in 82% of patients with primary ovarian carcinoma, and in 29% of those with benign ovarian tumors. The values from patients with ovarian carcinomas in partial or complete remission were compared with those from patients with progressive disease. The former group had elevated levels in 19% compared to 89% in the latter group. Fifty-four percent of the values in progressive cervical carcinoma and 41% of the levels in progressive endometrial carcinoma were greater than 35 U/ml. High CA 125 levels were found in the cytosol of placenta, ovarian carcinoma, cervical carcinoma, and in ascitic fluid; correlation with serum levels was satisfactory. Even though CA 125 is of limited specificity for ovarian cancer, serum levels are important for follow up care and for the early detection of recurrences.     

Clinical usefulness of serum sialyl SSEA-1 antigen levels in patients with epithelial ovarian cancer. Comparative effectiveness of sialyl SSEA-1 and CA 125

The serum levels of sialyl SSEA-1 antigen, a type 2 chain carbohydrate antigen detected using the monoclonal antibody FH-6, were elevated in 47.2% of patients with epithelial ovarian cancer, with the percent positivity increasing with the clinical stage. Of the histological type, it is interesting to note the relatively high sensitivity in patients with mucinous adenocarcinoma and clear cell carcinoma in contrast with the CA 125 antigen levels. Although the percentage of patients with ovarian cancer who had elevated sialyl SSEA-1 antigen levels is lower than that observed with elevated CA 125 antigen levels, the false-positive rate is significantly low in the sialyl SSEA-1 test. Serial sialyl SSEA-1 antigen levels obtained during follow-up were strong predictors of clinical outcome. The combined determination possible with sialyl SSEA-1 and CA 125 did not markedly increase the detection rate because of the overlap in the positivity. However, increased levels of both serum sialyl SSEA-1 antigen and CA 125 antigen indicated the presence of malignancies in pregnant women associated with ovarian tumors.