Usefulness of measurement of serum CA125 levels in diagnosing and treating endometriosis

We investigated the usefulness of the measurement of serum CA125 levels for the diagnosis and therapeutic monitoring of endometriosis. An additional study concentrated on the production of CA125. 1. Elevated levels of serum CA125 were noted in 52 of 66 patients with endometriosis in which the positive rate was 78.8% and mean was 119.8 U/ml. The mean value and positive rate of serum CA125 levels in patients with adenomyosis were higher than those in pelvic endometriosis. 2. The correlation between preoperative serum CA125 levels and the extracted tissue weight was statistically significant. The tissue concentration of CA125 of adenomyosis was 1,479.3 +/- 1,087.1 U/g and that of pelvic endometriosis was 309.7 +/- 23.1 U/g wet weight. 3. The serum CA125 levels in patients with adenomyosis fell postoperatively, and all were below 35 U/ml within two weeks. The serum CA125 levels were below 35 U/ml in 13 out of 15 patients (86.7%) with pelvic endometriosis treated with danazol and the change in the serum CA125 levels was closely related to the clinical course. 4. Clinicopathological states with a high level of serum CA125 were observed in patients with normal and ectopic pregnancy, puerperium, ovarian hyperstimulation syndrome (OHSS) and peritonitis. It was concluded that the measurement of serum CA125 levels was useful in the diagnosis and therapeutic monitoring of endometriosis, and CA125 might be produced and/or secreted not only from the endometrium but also from the peritoneum.     

CA 125 in the follow-up of patients with ovarian cancer

Three hundred and ninety-five CA 125 serum values of 72 patients with ovarian cancer were correlated with the clinical status. With a threshold value of 35 U/ml we found true negative values in 85% and true positive values in 93%. No correlation between preoperative CA 125 values and tumor stage was noted at primary surgery. During follow-up, 17 women had marker values between 35 and 65 U/ml. Three out of 7 women in clinical remission showed a value greater than 65 U/ml at subsequent follow-up and developed recurrent disease. In 8 patients out of 20 re-laparotomies, tumors with a maximum diameter of greater than 2 cm were confirmed with a preoperative serum CA 125 concentration greater than 65 U/ml. Two out of 3 patients with a tumor diameter less than 2 cm at re-laparotomy revealed CA 125 serum concentrations less than 35 U/ml. A false positive CA 125 value was found in one patient without demonstrable active disease. The calculated doubling time of the CA 125 values ranged between 23 and 173 days; the median value was 67 +/- 47 days. After 6.2 +/- 1.3 doubling times death ensued.     

CA 125 antigen is an effective diagnostic for external endometriosis

We measured serum levels of CA 125 in 26 patients with external endometriosis, using CA 125 RIA Kits. The normal range was instituted below 39 U/ml. The mean CA 125 level (+/- SD) was 55.1 +/- 24.9 U/ml in patients with external endometriosis, the positive rate being 71.4%. Considering the clinical stage of external endometriosis, the mean CA 125 level and positive rate increased to 64.5 +/- 23.2 U/ml and 93.3%, respectively. The CA 125 levels in these patients gradually decreased after surgery and/or Danazol treatment and the levels were below 39 U/ml within four weeks. Thus, progressive external endometriosis can be accurately diagnosed by determining the serum levels of CA 125, and appropriate clinical treatment designed.     

Elevated serum concentrations of CA-125 in patients with advanced endometriosis

CA-125 is a high-molecular-weight glycoprotein that is expressed on the cell surface of some derivatives of embryonic coelomic epithelium. Based on results of an immunoradiometric assay developed to detect CA-125 in peripheral blood, 82% of patients with ovarian cancer and less than 1% of apparently healthy controls have elevated peripheral blood levels of CA-125. Because endometriotic lesions are likely to be derivatives of embryonic coelomic epithelium, the authors investigated serum CA-125 levels in patients with endometriosis. Preoperative serum CA-125 concentrations were measured in 147 patients undergoing diagnostic laparoscopy or laparotomy. Serum CA-125 concentrations were elevated in patients with stage III or IV endometriosis, compared with controls with negative diagnostic laparoscopies (66.5 +/- 14.5 versus 8.20 +/- 0.59 U/ml, mean +/- standard error of the mean; P less than 0.001). Fifty-four percent of patients with stage III or IV endometriosis and 0% of the controls had CA-125 levels greater than 35 U/ml. Occasional patients with stage II endometriosis (13%), leiomyomata uteri (14%), and chronic pelvic inflammatory disease (5%) also had serum CA-125 concentrations greater than 35 U/ml. Immunocytochemical techniques demonstrated the presence of CA-125 on the cell surface of endometriotic lesions.     

Clinical use of CA 125 and its combination assay with other tumor marker in patients with ovarian carcinoma

The serum levels of CA 125 and CA 19-9 were determined by an immunoradiometric assay employing the monoclonal antibody OC 125 and anti-CA 19-9 antibody in 88 patients with ovarian carcinoma. When a cut-off value of CA 125 was set below 35 U/ml in the control group, serum elevated levels of CA 125 were found in 86.7% of the patients with surgically demonstrable ovarian serous cystadenocarcinoma, in 100% (4/4 cases) of clear-cell carcinoma, in 50% (2/4 cases) of endometrioid carcinoma, in 100% (5/5 cases) of undifferentiated carcinoma, and in 80% of the recurrent cases. Using a cut-off value of 37 U/ml, serum elevated levels of CA 19-9 were detected in 68.2% of mucinous cystadenocarcinoma, in 28.9% of serous cystadenocarcinoma, in 75% (3/4 cases) of metastatic ovarian carcinoma, and in 37.5% of the recurrent cases. A statistical analysis of the combination assay using CA 125, CA 19-9, tissue polypeptide antigen (TPA), immunosuppressive acidic protein (IAP), ferritin and CEA was carried out by multivariate method (discriminatory analysis) in 45 patients with ovarian carcinoma and 50 healthy subjects. As a result before treatment, positive rates of a single tumor marker were 79.7% with CA 125, 42.7% with CA-19-9, 73.1% with IAP, 61.7% with TPA, 64.3% with ferritin and 25.4% with CEA, respectively. A combination assay of these markers was useful for detecting identification of ovarian carcinoma, by which it gave a higher accuracy of ovarian cancer detection.     

Monitoring human ovarian carcinoma with a combination of CA 125, CA 19-9, and carcinoembryonic antigen

CA 125 and CA 19-9 are antigenic determinants associated with human epithelial ovarian carcinomas. Murine monoclonal antibodies have been raised against these determinants, and immunoradiometric assays have been developed to monitor antigen levels in the serum of cancer patients. This study was undertaken to determine whether concomitant measurement of CA 125, CA 19-9, and carcinoembryonic antigen would provide a more precise correlation with tumor progression or regression than could be obtained with any single assay. Among 105 patients with surgically demonstrable epithelial ovarian carcinoma, serum CA 125 levels were elevated (greater than 35 U/ml) in 83%, CA 19-9, levels (greater than 37 U/ml) in 17%, and carcinoembryonic antigen levels (greater than or equal to 2.5 ng/ml) in 37%. Within individual samples, no correlation was found among values for the three markers, but patients with elevated CA 19-9 levels also had increased levels of CA 125. At least one of the three markers was elevated in 90% of the subjects. When 41 patients were monitored serially over 2 to 60 months, alterations in CA 125 levels correlated with disease progression or regression in 94% of instances, whereas alterations in CA 19-9 levels correlated in 33% and alterations in carcinoembryonic antigen levels in 25% of instances. Concomitant measurement of CA 125, CA 19-9, and carcinoembryonic antigen did not prove superior to measurement of CA 125 alone in the monitoring of patients with epithelial ovarian carcinoma.     

CA 125 for the monitoring of ovarian carcinoma during primary therapy

Thirty-one patients with ovarian cancer were monitored with the CA 125 antigenic determinant in the interval between cytoreductive surgery and the completion of subsequent chemotherapy. Distinct CA 125 assay trends have emerged from prospective serial monitoring. Among patients who were clinically and surgically free of disease after the completion of cytoreductive chemotherapy, the CA 125 assay always fell to levels under 35 U/mL within the first three months of cytoreductive chemotherapy, and stayed at low levels. Patients with partial cytoreduction operations had decreases in serum CA 125 levels only if there was a response to further therapy. The rate of fall of the CA 125 levels correlated with clinical outcome. All 13 patients with serum CA 125 above 35 U/mL after three months of treatment invariably had persistent tumors after subsequent chemotherapy, whereas in patients showing reduction of the CA 125 to levels below 35 U/mL, there were no surgically detectable tumors. Measurement of CA 125 during treatment might permit an early change to alternative and optimal forms of therapeutic management. The CA 125 level three months after treatment appears to be a critical predictor of response to therapy.     

Changes in CA125 concentration in ovarian cancer patients during the remission state--mean attenuating curve and the effectiveness of surgery and chemotherapy

We have periodically monitored CA125 in 21 primary ovarian cancer patients who were clinically diagnosed as in the remission state after cytoreductive surgery and a combination chemotherapy 200 days after surgery. In this monitoring, the mean attenuating curve (exponential curve) of CA125 within 75 days after surgery was obtained, Y = 2.4831 exp (-0.11281 x 10-1X) [Y:log10 (CA125), X:days from the surgery]. According to this formula, the half life of CA125 is 11.5 days and CA125 is supposed to decrease to under 35U/ml in 42.1 days. In the patients whose preoperative CA125 was over 1,000U/ml (n = 8), the half life was 6.8 days and CA125 fell below 35U/ml within 45.8 days. In the rest of the patients, (35U/ml less than preoperative CA125 less than 1,000U/ml), these figures were 16.3 days and 38.2 days, respectively. Then in the patients whose tumors were completely resected (n = 13), the mean attenuating curve was Y = 2.3655 exp (-0.99935 x 10(-2)X), the half life was 13.6 days, and CA125 decreased to under 35U/ml in 42.7 days. After primary surgery, CA125 decreased to 50.0 +/- 54.2% of the preoperative concentration. Among 16 patients (without 5 P-MFC chemotherapy) 13 (13/16, 81.3%) showed CA125 under 35U/ml after 2 courses of chemotherapy. Thus, it became clear that CA125 decreases in the remission state of ovarian cancer.     

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.     

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.     

Serial measurement of CA 125 in patients with primary carcinoma of the fallopian tube

Serial assay of serum CA 125 was carried out in five patients with advanced primary carcinoma of the fallopian tube. Pretreatmental levels of these patients were elevated, ranging from 145 to 535 U/ml (305 +/- 140.1, mean +/- SD). All patients showed rapid decreases in response to treatment; however, reelevations were noted in two patients concomitant with recurrence. In the remaining three patients, who are alive with no evidence of recurrence at 52, 29, and 21 months, serum CA 125 levels remained below 5 U/ml after remission. These results suggest that CA 125 is useful in monitoring patients with primary carcinoma of the fallopian tube.     

CA125 Serum Levels and Secondary Laparotomy in Epithelial Ovarian Tumours

CA125 serum levels were assayed prior to 57 secondary laparotomies for ovarian epithelial tumours. Tumour was present in all 16 patients with an elevated level greater than 35 U/ml but the absence of tumour was incorrectly predicted in 15 of the 33 (45.5%) patients with CA125 levels less than 35 U/ml. For these patients the CA125 level was elevated in 14 of 20 (70%) with tumour greater than 1.5 cm, 1 of 7 (14.3%) with macroscopic tumour less than or equal to 1.5 cm and 1 of 4 (25%) with microscopic tumour. Tumour was resectable to less than or equal to 0.5 cm in 7 of 12 (58.3%) patients with CA125 less than 35 U/ml, 2 of 4 (50%) with CA125 in the range 35-100 U/ml and only 1 of 11 (9.1%) with CA125 greater than 100 U/ml (p less than .05). The CA125 level was elevated in 1 of 13 (7.7%) patients with less than 15 cm3 of tumour compared with 16 of 18 (88.9%) patients with 15 cm3 of tumour or more (p less than .0001). The correlation between the CA125 serum level and the tumour volume was almost statistically significant (r = +0.31, p = .053). The level of CA125 was normal in all 8 patients with mucinous tumours--4 of whom were found to have tumour at secondary surgery.(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。     

Analysis of CA 125 assay system and its diagnostic significance in gynecologic tumors

CA125 antigen levels were measured in patients with ovarian cancer (54 cases) by the RIA method using a monoclonal antibody OC125 and were examined as a marker for ovarian cancer. The upper normal limit of CA125 of 35 U/ml was derived from the mean value (15.7 U/ml)+2SD (9.3 U/ml) of CA125 in healthy controls. The mean value for CA125 in patients with ovarian cancer (1160 +/- 1850 U/ml) was statistically (p less than 0.001) higher than those of healthy controls, benign ovarian tumors (28 +/- 20 U/ml) and cervical cancers (226 +/- 526 U/ml). Elevated CA125 levels were also found in the early pregnant stage and endometriosis, but these cases showed not so high CA125 values as those of ovarian cancers. In addition, CA125 levels were not clearly affected by the menstrual cycle. Among ovarian malignancies, the elevated CA125 values were specifically demonstrated in serous cystadenocarcinoma (positivity 89%) and markedly low in mucinous cystadenocarcinoma (positivity 16%). No positive correlation of CA125 values with the clinical stage (FIGO) were found in any ovarian cancer patients. The rise and fall of CA125 levels corresponded closely with progression and regression of cancer patients with positive CA125 levels. In conclusion, serum CA125 determinations may be useful in patients with ovarian cancer (except for mucinous type) for diagnosis and for monitoring the results of the treatment.     

Comparison of CA 125 assays with abdominopelvic computed tomography and transvaginal ultrasound in monitoring of ovarian cancer

Objective: To compare serum CA 125 assays with computed tomography (CT) and transvaginal ultrasound (TVUS) for early detection of disease recurrence in patients with ovarian cancer. Methods: Sixty-two patients with nonmucinous epithelial ovarian cancer who had positive CA 125 levels (> 35 U/ml) were studied. We performed a retrospective review to determine the usefulness of serum CA 125 measurements. Setting the cut-off limit at either 35 U/ml or 16 U/ml, the accuracy of CA 125 measurements was compared with that of CT scanning, TVUS and operative findings at second-look laparotomy (SLL) in the early detection of recurrent tumors. Results: Compared with SLL, both the specificity and the positive predictive value of CA 125 measurements were 100% at 16 and 35 U/ml. The sensitivity and the negative predictive value were 30.8 and 71.9%, respectively, below 35 U/ml and 53.8 and 79.3%, respectively, below 16 U/ml. The false-negative rate of CT was 36.1%. When the cut-off limit was reduced from 35 to 16 U/ml, 57.1% of patients considered to be in remission were reclassified as having persistent disease. A complete response confirmed by CT did not represent remission: CA 125 levels were 7.5-fold higher at the time of re-evaluation by CT. TVUS also lagged behind CA 125 assays in detecting disease recurrence. The sensitivity of ultrasound appeared to be lower than that of CT because it failed to detect extrapelvic lesions. Conclusion: A screening threshold (cut-off level) of 16 U/ml for CA 125 should be used to detect recurrent serous ovarian adenocarcinoma. Although ultrasound is a convenient method of detecting intrapelvic lesions, and has cost benefits, CT is necessary to detect extrapelvic recurrence. Neither CT nor ultrasound are more accurate than serial CA 125 assays in detecting disease recurrence.     

175例子宫内膜异位症患者血清CA125水平的回顾性分析

目的:分析子宫内膜异位症患者合并子宫内膜息肉的情况,探讨血清CA125水平与痛经、内异症rAFS分期、病灶部位的相关性,为临床上更好地解读CA125水平提供依据。方法:回顾性分析2010年1月至12月我院术中或术后病理诊断为子宫内膜异位症的175例患者的临床资料。结果:(1)20.0%的子宫内膜异位症患者合并子宫内膜息肉;(2)36.6%的内异症患者有中、重度痛经,痛经程度与血清CA125水平无相关性;(3)Ⅰ期、Ⅱ期、Ⅲ期、Ⅳ期内异症患者的平均CA125水平分别为21.5U/ml、28.4U/ml、38.6U/ml、57.1U/ml,Ⅲ～Ⅳ期内异症患者血清CA125水平高于Ⅰ～Ⅱ期患者(P<0.05);(4)腹膜型、混合型、卵巢型内异症患者血清CA125的阳性率分别为21.4%、63.0%和67.4%,混合型、卵巢型内异症患者血清CA125阳性率显著高于腹膜型(P<0.001)。结论:血清CA125水平不能作为内异症合并子宫内膜息肉的预测指标;血清CA125水平可用于辅助鉴别内异症的分期和病灶部位,但是CA125对于内异症的早期诊断缺乏敏感性。     

Normal serum CA125 half-life and normal serum nadir CA125 level in patients with ovarian cancers

The normal serum CA125 half-life and distribution of the normal serum nadir CA125 value in patients with epithelial ovarian carcinoma (EOC) have not been determined yet. Among patients with EOC, 41 patients met the inclusion criteria of the present study: the patients that underwent complete cytoreductive surgery and six cycles of platinum-containing chemotherapy, and who had no recurrent disease more than five years. Serum CA125 half-life (T1/2) during primary surgery and primary chemotherapy was calculated and serum nadir CA125 level was evaluated by logarithmic-transformed serum CA125. Median value of nadir CA125 was 7 U/ml (range 3-20 U/ml), and the mean ln (serum nadir CA125) was 1.96 +/- 0.45. Mean T1/2 was 10.4 days in all patients, and T1/2 value was associated with the preoperative serum levels of CA125. Predicted slope of CA125 regression curve was also influenced by the preoperative CA125 value. The present study provides fundamental information with regard to normal half-life time and normal nadir of CA125 in EOC patients.     

CA 125 in peritoneal fluid: reliable values at high dilutions.

Forty-three samples of peritoneal fluid from women undergoing laparotomy or laparoscopy for various gynecologic diseases were examined to determine and characterize CA 125 antigen. The data were compared with the corresponding serum levels. CA 125 levels in undiluted peritoneal fluid ranged between 41-301 U/mL and were significantly higher than levels in serum, except in cases of ovarian carcinoma. However, when CA 125 of peritoneal fluid was measured at dilutions greater than 1:50, higher antigen levels were measured (1120-31,500 U/mL), with the highest CA 125 values in patients with ovarian carcinoma. Measurements at dilutions of less than 1:50 were also affected but did not show any decreased binding of the antigen. Immunoblotting analysis of serum and peritoneal fluid indicated the presence of two main bands in each. The monoclonal antibody OC 125 reacted strongly with peritoneal fluid CA 125, in agreement with the CA 125 values obtained by immunoradiometric assay using high dilutions. These data suggest that CA 125 measurements in peritoneal fluid are unreliable unless the samples are diluted 1:50 or more. Furthermore, the statistical difference found between patients with benign and malignant tumors and those with leiomyomata uteri and controls suggests that diluted peritoneal fluid could have a role in identifying abnormal antigen levels.     

CA 125 in serum, peritoneal fluid, active lesions, and endometrium of patients with endometriosis

Ca 125 levels in serum and peritoneal fluid were measured in 39 patients with endometriosis and 18 patients with normal pelvic anatomy at laparoscopy, and the presence of this antigen in endometriotic tissue and endometrial mucosa was also investigated. Serum CA 125 concentrations were elevated in patients with Stage III or IV endometriosis compared with control subjects (32.9 +/- 11.2 versus 16.4 +/- 8.9 U/ml, means +/- SD; p less than 0.001). CA 125 values were greater than 35 U/ml in 36.8% of women with Stage III or IV endometriosis and in none of the control subjects. No significant differences in CA 125 levels in peritoneal fluid were found between patients with endometriosis and control subjects. The immunohistochemical studies found CA 125 in 10% of the endometriotic lesions and 37.5% of the endometrial samples of patients with endometriosis and in 33.3% of the endometrial samples of control subjects.     

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.