Evaluation of tumour markers in molar pregnancy

METHODS: Circulating CA 125, CA 19-9, CA 15-3 and carcinoembryonic antigen (CEA) levels were studied in sixty patients with hydatidiform mole and in twenty normal pregnant women of a corresponding duration of pregnancy. DISCUSSION: Serum levels of CA 125, CA 15-3 and CEA are not affected by molar pregnancy. The mean level of CA 19-9 in maternal serum is significantly lower in cases of molar pregnancy when compared with cases of normal pregnancy. The amnion cell origin of CA 19-9 could explain the statistically significant difference between cases of therapeutic abortion and cases of HM (complete HM lacks amniotic membrane).     

Preevacuation Serum CA 125 in Complete Hydatidiform Mole

Studies on CA 125 in hydatidiform mole are limited. The objective of this study was to measure the preevacuation serum CA 125 level in patients with complete hydatidiform mole and to determine whether it could predict the later development of persistent trophoblastic disease. Preevacuation serum CA 125 levels were immunoradiometrically measured in 69 patients with histologically confirmed complete hydatidiform mole. The mean (range) serum CA 125 level was 63.7 (10.5–404.7) U/ml. Using 35 U/ml as the cutoff point, the elevated CA 125 levels were observed in 53.6% (37/69) of the patients. The mean serum CA 125 level of patients who later developed persistent trophoblastic disease was not significantly higher than that of those who had benign course (78.9 vs 52.6 U/ml,P> 0.05). In conclusion, the preevacuation serum CA 125 level was elevated in about half of patients with complete hydatidiform mole and it could not be used to predict the subsequent development of persistent trophoblastic disease.     

Maternal serum Ca125 and Ca15-3 antigen levels in normal and pathological pregnancy

OBJECTIVE: To evaluate the value of maternal serum CA125 and CA15-3 concentrations for discriminating pathological from normal pregnancies. METHODS: Serum samples from 120 women, in whom pregnancy outcome was pathological, i.e. spontaneous abortion, fetal death, intrauterine growth retardation, chromosomal and structural abnormalities, and (pre)eclampsia, were assessed for CA125 and CA15-3 and compared with levels found in 350 women with a normal pregnancy outcome matched for age and duration of pregnancy. RESULTS: Maternal CA125 serum values were significantly higher in the first and the third trimester of pregnancy (median 23.0 and 21.0 U/ml; p < 0.00001 and p < 0.001, respectively), compared to those in the second trimester (median 14.0 U/ml), but not significantly different from those obtained in pathological pregnancies. Maternal serum CA15-3 values were significantly higher during the third trimester (median 26.0 U/ml) compared to the first and second trimester of pregnancy (median 14.0 and 15.0 U/ml; p < 0.0001); CA15-3 serum levels in normal and pathological pregnancies showed no significant difference. CONCLUSION: Maternal serum levels of CA125 are higher during the first and third trimester of pregnancy. CA15-3 maternal serum levels are higher during the third trimester compared to the first and second trimester. Maternal CA125 and CA15-3 serum levels showed no relation with a pathological outcome of pregnancy.     

Maternal CA 125 serum level in intrauterine pregnancy and abortion in the first trimester

OBJECTIVE: Maternal CA 125 levels are supposed to rise in pregnancies complicated by vaginal bleedings in dependence to the extent of decidual disruption which is directly related to the outcome of pregnancy. MATERIAL AND METHODS: The prognostic value of maternal CA 125 serum measurement was investigated in 239 women with a first trimester intact pregnancy, imminent, incomplete, complete or missed abortion. RESULTS: 43.9% of the CA 125 serum levels were without normal range (> 20 U/ml). Mean CA 125 serum levels were higher in patients with incomplete (52.4 +/- 67.4 U/ml), complete (34.3 +/- 46.1 U/ml), and imminent abortion (33.0 +/- 45.8 U/ml) as compared with normal pregnancies (28.9 +/- 28.8 U/ml) and missed abortion (23.5 +/- 21.5 U/ml). CA 125 levels in first trimester pregnancies tended to be higher in patients with vaginal bleedings than in patients without bleeding (40.5 U/ml +/- 55.0 vs. 28.9 U/ml +/- 28.8; p = 0.65). CONCLUSIONS: For clinical use CA 125 serum measurement is not relevant. First trimester CA 125 measurement can not serve as an accurate predictor of pregnancy outcome due to the wide overlap of ranges.     

Measurement of the Beta - Subunit of Chorionic Gonadotrophin in Uncomplicated, Complicated, and Molar Pregnancies

Summary: The beta-subunit of chorionic gonadotrophin (HCG-β) was measured in serum by radioimmunoassay in patients with uncomplicated, complicated, and molar pregnancies. In normal pregnancy, HCG-β was just detectable at levels of less than 10 ng per ml at 4 weeks of amenorrhoea; the levels increased rapidly to a peak mean value of 135.1 ng per ml at 9–10 weeks. Serum levels in patients with abortion or tubal ectopic pregnancy were much lower for the period of amenorrhoea, and results were negative for all patients who were not found to be pregnant. Serum levels were greatly elevated, often exceeding 1,500 ng per ml, in patients with hydatidiform mole. The majority of patients with molar pregnancies showed levels exceeding 750 ng per ml, whereas the highest level in patients with normal pregnancy was 325 ng per ml. The use of serial HCG-β levels provides a sensitive means of follow-up of hydatidiform mole, being able to distinguish the disease undergoing spontaneous regression from residual or metastatic disease.     

The prognostic significance of maternal serum CA125 measurement in threatened abortion.

The prognostic predictive value of maternal serum CA125 measurement was investigated in 25 cases of threatened abortion. The women were non-smoker, had a ultrasonographically verified viable single fetus, and the gestational ages ranged from 7 to 12 weeks. Twenty-five healty pregnant women, with the same characteristics were used as the control group. The overall abortion rate was found to be 20% (5/25) in the study group. In serial measurements the mean serum CA125 level of the patients with an unfavorable pregnancy outcome was significantly higher than that of the patients with a favorable outcome. When the cut-off level of maternal serum CA125 was taken as > 65 U/ml in the first and > 60 U/ml in the second measurements of the study group, the risk of termination of the pregnancy by spontaneous abortion was 83.3% in the patients with elevated serum CA125 levels. No statistically significant difference was observed with respect to the duration of vaginal bleeding between the aborters and the patients with a favorable outcome. Nevertheless, when vaginal bleeding had been present for 3 days or more and there was high maternal serum CA125 activity, the abortion risk was found to be 100% (3/3). These findings suggest that the maternal serum CA125 measurement in threatened abortion can be useful to determine the extent of decidual destruction which is directly related to the outcome of pregnancy.     

Studies on serum CA125 levels in pregnant women

To confirm the change in serum CA 125 levels in cases of pregnancy, we measured serum CA 125 levels in 234 normal pregnant women, 40 postpartum women and 14 abnormal pregnant women (12 of IUFD and 2 of H. mole), using an RIA kit. The mean CA 125 level (+/- S.D.) and positive ratio (greater than 34U/ml) for pregnant women at 4-11 weeks of gestation were 65.0 +/- 77.3 U/ml and 64.6%, respectively, being the highest values in all the groups. On the contrary, those for pregnant women at 12-23 weeks of gestation were 22.3 +/- 10.6 U/ml and 12.7%, respectively, the lowest in all gestational groups. Changes in serum CA 125 levels in normal pregnant women showed a trend toward decrease, as gestation advanced. But the CA 125 levels for women at postpartum showed a slight trend toward increase. The mean CA 125 level (+/- S.D.) for 12 patients with IUFD was 392.5 +/- 275.8 U/ml and that for 2 patients with H. mole was 65.0 +/- 15.0 U/ml. Serum CA 125 levels for patients with IUFD were higher than that in cases of normal pregnancy. When utilizing CA 125 as a marker for ovarian cancer, the influence of pregnancy must be considered. And it indicates that CA 125 can be used as an aid to the diagnosis of IUFD in serous cases.     

Prognostic value of repeated serum CA 125 measurements in first trimester pregnancy.

OBJECTIVE: To assess the diagnostic value of maternal CA 125 in patients with symptomatic first trimester pregnancy and to evaluate the prognostic significance of CA 125 versus beta-hCG in early pregnancies with intact fetal heartbeat, complicated by vaginal bleeding. STUDY DESIGN: Two prospective open-label studies with longitudinal follow-up in the second trial. SETTING: Academic Department of Obstetrics and Gynecology, University of Cologne. PATIENTS: Study 1: 168 patients presenting between gestational weeks 6 and 12 with: extrauterine pregnancy, 29; missed abortion, 50; incomplete spontaneous abortion, 38; imminent abortion, 33; and normal pregnancy (no history of endometriosis or ovarian mass), 18. Study 2: Fifty consecutive patients with vaginal bleeding during gestational weeks 6-12 all of whom having demostrable fetal heartbeat. Eighteen patients finally aborted whereas the remainder had normally continuing pregnancy until term. MAIN OUTCOME MEASURE: Study 1: Single serum determinations of CA 125 and beta-hCG were correlated with the different disorders observed. Study 2: Two sequential measurements of serum CA 125 and beta-hCG performed within a 5-7 days interval were related to the outcome of pregnancy as indicated by changes of the ultrasound presentation, miscarriage, future hospitalization, or delivery. RESULTS: Study 1: Patients with vaginal bleeding generally had higher median CA 125 values (38 IU/ml; range 1.3-540) compared to non-bleeding patients (17.8 IU/ml; range 1.0-157). No statistically significant differences in regard to median serum CA 125 levels between symptomatic and normal pregnancies occurred: normal pregnancy, 25.5 IU/ml (range 3.2-97); ectopic pregnancy, 26 IU/ml (range 1.3-157); missed abortion, 19.1IU/ml (range 1-242); threatened abortion, 48 IU/ml (range 5.2-540); spontaneous abortion, 40 IU/ml (range 5.4-442). Study 2: Initial CA 125 levels did not differ significantly between both groups of patients with 27/32 non-aborters and 13/18 aborters showing concentrations below 65 IU/ml. After 5-7 days, CA 125 in all patients who eventually aborted remained high or increased whereas non-aborters all had constantly low or steeply declining CA 125 measures. beta-hCG increased in all non-aborters but also in 13/18 aborters during the 5-7 day interval. CONCLUSION: Single serum measurements of CA 125 in symptomatic first trimester pregnant patients failed to discriminate spontaneous abortion, ectopic or normal pregnancies. However, sequential determinations of maternal CA 125 measurements appear to be a highly sensitive prognostic marker in patients with viable pregnancy at risk for abortion.     

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.     

Serum CA 125 levels in early pregnancy and subsequent spontaneous abortion

CA 125 has been found in high concentrations in human amniotic fluid throughout gestation, with significant quantities seen in the decidua and chorion. Because disruption of the epithelial basement membrane of the fetal membrane or the decidua could theoretically lead to a rise in maternal CA 125 levels, this increase may be a predictor of subsequent spontaneous abortion of the fetus. A study was initiated to investigate whether a sudden rise in the serum CA 125 level might predict spontaneous first-trimester abortions. CA 125 levels of 101 pregnant women were evaluated 18-22 days from conception and 6 weeks from conception (a frequent time for spontaneous abortion) to determine whether there is a sudden increase (from baseline or early trimester levels) during the middle or late first trimester immediately before or at the time of abortion. The results indicated that although there was a definite correlation found between elevation of CA 125 and spontaneous abortion, the higher levels occurred early in the first trimester whereas the majority of abortions did not occur until much later, after fetal viability was established. Six of ten women with CA 125 levels of 150 U/mL or greater aborted, compared with four of 92 women with CA 125 levels less than 150 U/mL. One of 11 women pregnant after in vitro fertilization had a CA 125 level above 150 U/mL, and she aborted.     

The distribution of CA 125 in the reproductive tract of pregnant and non-pregnant women

Summary. Investigation of serum and tissue homogenates obtained from first, second and third trimester pregnancies, and from nonpregnant women, has provided further insight into the possible origin of the CA 125 antigen. Serum CA 125 levels were higher in the first trimester (median 53.6 U/ml, range 15.6.268.3 U/ml) than in nonpregnant women (median 19.3 U/ml, range 7.2.27.0 U/ml) and later in pregnancy (second trimester: median 18.5 U/ml, range 12.0.25.1 U/ml, third trimester: median 19.2 U/ml, range 16.8.43.8 U/ml) (P<0.05) but were two orders of magnitude less than in second trimester amniotic fluid (median 4825 U/ml, range 3200.9300 U/ml). Fetal serum CA 125 activity was consistently <20 U/ml. The highest tissue levels of CA 125 were detected in first trimester decidual homogenate (median 4547 U/ 100 mg, range 340.4–20 851 U/100 mg) and were greater than in nonpregnant endometrium (median 388 U/100 mg, range 100.9–3341 U/100 mg) ( P <0.01) and term decidua (median 116 U/100 mg, range 32.7–449.9 U/100 mg) (P<0.01). These observations suggest that CA 125 is synthesized by normal endometrium and decidua and that increased CA 125 activity during pregnancy is of decidual origin.     

Serum concentration of CA-125 during the first trimester of normal and abnormal pregnancies

A prospective study was initiated to closely examine maternal serum concentrations of CA-125 during the early first trimester of normal and abnormal pregnancies. Sequential serum specimens were obtained from 43 women with a normal intrauterine pregnancy, 20 with a surgically confirmed ectopic gestation and 10 whose pregnancies ended in spontaneous abortion. In normal pregnancies the CA-125 levels increased significantly from the first week after the missed menses (39.9 +/- 8.2 U/mL [mean +/- SEM]) to the second week (48.3 +/- 6.9 U/mL) (P less than .05) and from the second to the third week (62.5 +/- 9.8) (P less than .05). After the third week after the missed menses the mean CA-125 serum concentrations plateaued, but levels observed during the fourth (59.6 +/- 8.8 U/mL) and fifth (48.8 +/- 7.2 U/mL) weeks were still significantly greater than at week 1. In addition, the mean CA-125 concentrations were significantly higher in normal pregnancies than in ectopic gestations during the second, third and fourth weeks after the missed menses. Although there was a tendency for the CA-125 levels to be lower in women who had a spontaneous abortion when compared to normals, these differences were not statistically significant. Serum levels of CA-125 may prove useful in monitoring early pregnancy.     

The distribution of CA 125 in the reproductive tract of pregnant and non-pregnant women

Investigation of serum and tissue homogenates obtained from first, second and third trimester pregnancies, and from non-pregnant women, has provided further insight into the possible origin of the CA 125 antigen. Serum CA 125 levels were higher in the first trimester (median 53.6 U/ml, range 15.6-268.3 U/ml) than in non-pregnant women (median 19.3 U/ml, range 7.2-27.0 U/ml) and later in pregnancy (second trimester: median 18.5 U/ml, range 12.0-25.1 U/ml, third trimester: median 19.2 U/ml, range 16.8-43.8 U/ml) (P less than 0.05) but were two orders of magnitude less than in second trimester amniotic fluid (median 4825 U/ml, range 3200-9300 U/ml). Fetal serum CA 125 activity was consistently less than 20 U/ml. The highest tissue levels of CA 125 were detected in first trimester decidual homogenate (median 4547 U/100 mg, range 340.4-20 851 U/100 mg) and were greater than in non-pregnant endometrium (median 388 U/100 mg, range 100.9-3341 U/100 mg) (P less than 0.01) and term decidua (median 116 U/100 mg, range 32.7-449.9 U/100 mg) (P less than 0.01). These observations suggest that CA 125 is synthesized by normal endometrium and decidua and that increased CA 125 activity during pregnancy is of decidual origin.     

Mechanism and clinical significance of elevated CA 125 levels in the sera of pregnant women

To clarify the mechanism of CA 125 elevation in maternal sera, serum levels of CA 125 and CA 19-9 were measured in 122 apparently healthy pregnant women (fifth to fortieth week of gestation) and 50 postpartum women (26 term deliveries and 24 second-trimester induced abortions). Serum levels of CA 125 showed an initial increase by the tenth week and then decreased to less than 35 U/ml, remaining below this level until delivery. However, within 1 hour after term delivery or second-trimester induced abortion, the CA 125 levels showed a second increase and decreased rapidly thereafter. In contrast, serum levels of CA 19-9 did not change significantly during these periods. Combined with our previous finding that the decidua contains abundant CA 125 but little CA 19-9, these results indicate that the elevated CA 125 levels in maternal sera originate from the decidual cells affected by chorionic invasion or the placental separation.     

Quantitative analysis of a novel pregnancy-associated protein in trophoblastic diseases,normal pregnancy and healthy female subjects

Summary By means of the Laurell rocket technique, a novel pregnancyassociated protein was measured in the serum of patients with trophoblastic diseases as well as in pregnant women. In 52 normally-menstruating women, the serum levels were below the detection limit in 40 (76.9%); 50 women (96.2%) had levels of less than 2.0 U/ml, and none had levels above 2.1 U/ml. Of 25 patients with a hydatidiform mole, 23 (92.0%) had elevated levels (>2.2 U/ml). In 84 healthy pregnant women, the levels rose from being undetectable before 5 weeks to a plateau in the second trimester. The results suggest that the appearance of this protein in serum is associated with trophoblastic activity.     

The tumor marker CA 125 is a common constituent of normal cervical mucus

The presence of the tumor marker CA 125 was studied in the cervices of healthy women. Immunohistochemical staining of normal cervical tissue demonstrated the presence of CA 125 in the tall columnar cells of the endocervical epithelium but not in the ectocervical squamous epithelium. We measured very high levels of CA 125 in liquefied cervical mucus from women with regular menstrual cycles. At midcycle, levels ranged from 14,200 to 153,000 U/ml (n = 13) in cervical mucus, while normal levels less than 35 U/ml were found in the corresponding serum samples. Levels of CA 125 in cervical mucus are comparable to the high levels found in cyst fluids from ovarian tumors (median 24,600 U/ml, n = 25). When secretion of cervical mucus was stimulated by ethinyl estradiol, equally high levels were found (7900 to 138,000 U/ml, n = 10). We conclude that the tumor marker CA 125 is synthesized and secreted by normal endocervical cells. Apparently an effective barrier exists between the endocervical mucosa and the circulation.     

Comparison between serum CA 125 and CA 19-9 assays and tissular OC 125 and 1116NS 19-9 reactivity in malignant and benign ovarian tumors.

This preliminary study included 25 patients with primary epithelial ovarian cancer (EOC) (18 serous, 3 serous-mucinous, 1 endometrioid, 2 undifferentiated carcinomas and 1 malignant Brenner carcinoma); 2 patients with borderline ovarian tumors and 20 patients with benign ovarian tumors (9 benign cystic teratomas, 6 serous cystoadenomas and 5 mucinous cystoadenomas). Blood samples for the measurement of CA 125 and CA 19-9 were drawn from all patients before surgery. Serum CA 125 (Reference Value-RV = 65 U/ml) and CA 19-9 (RV = 40 U/ml) were measured with IRMAs using the monoclonal antibodies (MoAbs) OC 125 and 1116NS 19-9. The same antigens were detected on paraffin-embedded tissue sections by immunocytochemistry with the avidin-biotin complex method employing the same MoAbs used for serum IRMAs. Among the 25 patients with EOC serum CA 125 levels were elevated in 20: tissular OC 125 reactivity was observed in 15 (75%) of them. Of the 5 EOC patients with normal CA 125 levels, 4 showed OC 125 reactivity. Only 2 of the 25 EOC patients had elevated serum CA 19-9 levels: one of them had tissular 1116 NS 19-9 reactivity. Among the 23 patients with normal serum CA 19-9 levels only 5 had immunocytochemical reactivity for this antigen. The 2 patients with borderline ovarian tumors had negative serum CA 125 and CA 19-9 assay: tissular OC 125 reactivity was observed in both patients, while 1116 NS 19-9 reactivity was detected in only one.(ABSTRACT TRUNCATED AT 250 WORDS)     

血清和腹腔液CA125测定与子宫内膜异位症诊断的相关分析

目的:探讨不孕症患者术前血清及术中腹腔液CA125浓度与诊断子宫内膜异位症(EM)的关系。方法:对129例因疑输卵管性不孕而行腹腔镜或宫腹腔镜联合手术的患者,于术前抽取血清,术中抽取腹腔液测CA125浓度。根据血清CA125值分为<10U/ml、10-15U/ml、16-34U/ml和≥35U/ml4组,分析各组血清和腹腔液中CA125浓度与EM诊断的相关性。结果:血清CA125水平<10U/ml和≥16U/ml时,EM的诊断符合率分别为9.09%和89.55%,两组比较有显著差异(P<0.01)。腹腔液<800U/ml和≥800U/ml的EM诊断符合率分别为19.23%和94.80%,两组比较有显著差异(P<0.01)。血清CA125≥10U/ml结合腹腔液CA125≥800U/ml的诊断符合率为93.42%。结论:血清CA125≥10U/ml结合腹腔液CA125≥800U/ml对EM的诊断有重要参考价值。     

Can a single serum CA125 assay predict the outcome of threatened abortion?

Earlier work suggested that high levels of CA125 could be detected in the sera of women with threatened abortion. In this study, we used CA125 as a method of anticipating outcome in cases of threatened abortion and compared the results with ultrasonic findings. Three groups of patients were studied.(1) 57 women who threatened to abort, but whose pregnancy continued.(2) 43 women with a threatened abortion, who subsequently aborted, and (3) 50 normal women who had no bleeding in early pregnancy. There was a highly significant increase in serum CA125 in women who aborted compared with the other two groups (P<0.001). The results compared well with conventional ultrasound and serum CA125 may be developed as a cheap, sensitive and specific predictor of outcome in cases of threatened abortion.     

Measurement of CA-125 in trophoblastic disease

OBJECTIVES: Physicians treating hydatidiform mole are still seeking means of identifying those patients who will require chemotherapy. The standard accepted method is to follow human chorionic gonadotropin levels but CA-125 measurement has been suggested as a supplement that may be clinically useful. This study was undertaken to validate or refute the one previous study that addresses this issue. CA-125 was measured at the time of hydatidiform mole evacuation to determine (1) whether it would predict the need for chemotherapy and (2) whether it correlated with human chorionic gonadotropin and tumor load in following patients with hydatidiform mole and metastatic gestational trophoblastic disease. PATIENTS AND METHODS: CA-125 was measured in serial weekly samples selected from diagnostic groups of patients with trophoblastic disease. Sixteen patients had hydatidiform mole with spontaneous resolution, fourteen had nonmetastatic gestational trophoblastic tumor, and four had low-risk metastatic disease. Six patients had high-risk metastatic disease. Ten patients had partial hydatidiform mole and one of these required chemotherapy. One patient had primary ovarian choriocarcinoma and three had placental site tumor. RESULTS: The mean preevacuation CA-125 among the 15 patients with complete hydatidiform mole was 40.9 U/ml: 52.5 U/ml for 5 patients who required chemotherapy and 36.2 U/ml for 10 patients who did not require chemotherapy. There was no statistical difference between these values. There was no correlation of CA-125 with hCG. Frequently CA-125 became negative when hCG was still elevated. Among six patients with high-risk disease, CA-125 was elevated in four but in all six patients hCG remained elevated when CA-125 became negative. In nine patients with partial hydatidiform mole CA-125 was elevated prior to mole evacuation and then became negative. The patient with a tetraploid conceptus who required chemotherapy had negative CA-125. With placental site tumor CA-125 was negative, but it was elevated with ovarian choriocarcinoma. CONCLUSION: CA-125 levels do not provide reliable information in the management of patients with gestational trophoblastic disease.