The concomitant determination of different tumor markers in patients with epithelial ovarian cancer and benign ovarian masses: relevance for differential diagnosis.

The serum levels of CA 125 (cutoff limit, 65 U/ml), CA19.9 (cutoff, 40 U/ml), CA 15.3 (cutoff, 32 U/ml), CA72.4 (cutoff, 3.8 U/ml), and TATI (cutoff, 22 ng/ml) were preoperatively measured in 90 patients with epithelial ovarian cancer and in 254 patients with benign ovarian pathology. CA125 had a sensitivity of 75.6%, a specificity of 86.6%, and a diagnostic accuracy of 83.7% for epithelial ovarian cancer; CA19.9 had a sensitivity of 35.6%, a specificity of 81.1%, and a diagnostic accuracy of 69.2%; CA15.3 had a sensitivity of 57.1%, a specificity of 93.9%, and a diagnostic accuracy of 84.6%; CA72.4 had a sensitivity of 70.7%, a specificity of 91.8%, and a diagnostic accuracy of 86.2%; and TATI had a sensitivity of 47.3%, a specificity of 95.3%, and a diagnostic accuracy of 82.9%. CA 125 was the most sensitive marker for nonmucinous tumors, while CA19.9 and CA72.4 were the antigens more frequently expressed by mucinous malignancies. The sensitivities of serum CA 125 (81.1% vs 50.0%; P = 0.01) and TATI (55.2% vs 18.8%; P = 0.02) were higher in patients above 50 years of age than in younger patients while specificities were quite similar in both age groups. The association of serum CA125 and CA19.9 had a significantly higher sensitivity (93.2% vs 81.1%; P = 0.03) and a slightly lowered specificity (78.9% vs 86.0%; P = 0.46) than CA125 assay alone in the differential diagnosis of ovarian masses in patients above 50 years of age.     

Intracystic evaluation of tumor markers in benign and malignant ovarian pathology

OBJECTIVE: To evaluate, in patients with benign and malignant ovarian cysts, serum samples and ovarian intracystic fluids for the presence of tumor markers such as CA 125, CA 15.3, tissue polypeptide antigen (TPA), CA 19.9 and the carcinoembryonic antigen (CEA). MATERIAL AND METHOD: We studied overall 64 patients with ovarian pathology. Sixteen patients were affected by functional cysts, 28 women by benign cystic tumors and 20 by cystoadenocarcinomas. RESULTS: Average serum levels of all but CA 15.3, TPA and CEA tumor markers of benign cystic ovarian tumors were higher than those of functional cysts. All but CA 19.9 mean intracystic fluid markers levels were more elevated in benign tumors than in functional cysts. In patients with malignant cystic tumors, all but CEA mean serum marker levels were higher than those of benign tumors; furthermore even all mean intracystic levels of markers were more elevated than those of benign tumors. CONCLUSION: This study confirmed the high positivity of tumor markers such as CA 125, CA 15.3, TPA, CA 19.9 and CEA in both the serum and intracystic fluid of patients with malignant epithelial ovarian tumors.     

A comparative evaluation of the ability of serum CA 125, CA 19-9, CA 15-3, CA 50, CA 72-4 and TATI assays in reflecting the course of disease in patients with ovarian carcinoma

The Authors compared the ability of serum CA 125, CA 19-9, CA 15-3, CA 50, CA 72-4 and Tumor-Associated Trypsin Inhibitor (TATI) assays in reflecting the disease course in a group of 27 patients with ovarian carcinoma. Before initial surgery, elevated levels of CA 125 (greater than 65 U/ml) were found in 27 patients, of CA 19-9 (greater than 40 U/ml) in 7, of CA 15-3 (greater than 32 U/ml) in 17, of CA 50 (greater than 20 U/ml) in 7, of CA 72-4 (greater than 3.8 U/ml) in 20, and of TATI (greater than 22 ng/ml) in 13. For each marker, only patients with elevated antigen levels at diagnosis were considered. CA 125, CA 19-9, CA 15-3, CA 50, CA 72-4 and TATI levels correlated with disease regression, stability or progression in 123/147 (83.7%), 24/34 (70.6%), 57/87 (65.5%), 26/38 (68.4%), 87/120 (72.5%), 33/75 (44.0%) instances respectively. Alterations in CA 125 levels correlated with disease status better than alterations in each other antigen levels. However serial measurement of the other tumor markers could be of help in the monitoring of patients with normal CA 125 values before initial surgery.     

CA 125, placental alkaline phosphatase, and tissue polypeptide antigen in the monitoring of ovarian carcinoma. A comparative study of three different tumor markers

Three different tumor markers, placental alkaline phosphatase (PLAP), tissue polypeptide antigen (TPA), and cancer antigen 125 (CA 125), were measured in serum samples obtained during chemotherapy in 57 ovarian carcinoma patients. At the start of chemotherapy, 37, 63, and 77% had elevated serum values of PLAP, TPA, and CA 125, respectively. During chemotherapy, changing PLAP serum levels reflected disease regression and, later, progression in only 2 patients. TPA serum levels reflected the disease course in 15 patients and CA 125 in 28 patients. Rising CA 125 values predicted disease progression in 12 patients for a median of 2 months. At second-look laparotomy, all 11 patients with pathological complete response were marker negative. In the remaining 46 patients with residual or progressive disease, 27, 50, and 61% had elevated serum levels of PLAP, TPA, and CA 125, respectively. None of the markers reflected microscopic disease or pure carcinomatosis. For management decisions, CA 125 was clearly the most useful of the markers. In this study no further information was gained from the other two markers.     

Tumor tissue CA125 in ovarian carcinoma patients with normal serum levels

A good correlation between elevated serum CA125 and its immunolocalization in ovarian tumor tissue has been reported. This study was undertaken in order to assess the presence of CA125 in tumor tissue obtained from ovarian carcinoma patients with normal serum levels. Eleven such ovarian carcinoma patients (nine of them serous) were identified. In seven the level was normal prior to the initial operation, and in four, prior to a positive second-look operation. Immunohistochemical staining of paraffin sections for CA125 was positive in seven of the tumor tissue samples. Tumor tissue of most ovarian carcinoma patients with a preoperative normal serum CA125 contains the antigen, but an undetermined mechanism prevents elevated serum levels.     

组织多肽抗原在卵巢癌诊断及监测中的应用

目的评价组织多肽抗原（ＴＰＡ）在卵巢癌诊断和监测中的临床价值。方法应用放射免疫方法测定了２４例正常妇女、２７例妇科良性疾患及６０例卵巢癌患者的血清ＴＰＡ及ＣＡ１２５值并进行比较分析。结果ＴＰＡ在卵巢上皮性癌患者中的异常检出率为８２％,ＣＡ１２５为７０％,二者总的异常检出率为９２％。在绝大多数正常妇女和卵巢良性肿瘤患者中,ＣＡ１２５和ＴＰＡ在正常范围。作为卵巢癌相关标志物,ＴＰＡ与ＣＡ１２５具有相似敏感性。１９例动态观察结果显示,ＴＰＡ和ＣＡ１２５二者与病情转归是一致的。结论ＴＰＡ和ＣＡ１２５联合应用对卵巢癌的鉴别诊断及提高总的异常检出率具有价值。     

CA125 in peritoneal fluid of ovarian cancer patients.

The presence of CA125 was assessed in peritoneal fluid from 70 patients with ovarian cancer and 32 control patients. The follow-up period ranged from 39 to 89 months (median, 56 months). The cutoff for normal peritoneal fluid CA125 levels was determined to be 250 U/ml. A positive correlation between the serum and peritoneal fluid CA125 levels was observed (P less than 0.001). Peritoneal fluid levels were higher than serum levels in all patients. Patients with evidence of active ovarian cancer showed higher peritoneal fluid CA125 levels than the control patients (P less than 0.001). Peritoneal fluid CA125 levels correlated inversely with survival (P = 0.004). The peritoneal fluid CA125 levels were higher in patients with bulky tumor than in those with small (less than 1 cm) tumors (P less than 0.001). Eight out of twenty-six patients with active cancer and available peritoneal cytology had a negative peritoneal cytology. Three of these patients showed elevated peritoneal fluid levels. Three patients out of twenty-four showed elevated peritoneal fluid CA125 levels at second-look laparotomy. These 3 patients had negative biopsies at second-look surgery, but relapsed during the observation period. At second-look laparotomy an elevated peritoneal fluid CA125 level may imply a bad prognosis, but a normal level does not exclude the presence of disease.     

Evaluation of two new assays for tumor-associated antigens, CASA and OSA, found in the serum of patients with epithelial ovarian carcinoma--comparison with CA125.

Two new assays have been developed to measure tumor-associated antigens designated ovarian serum antigen (OSA) and cancer-associated serum antigen (CASA). Both assays are dual epitope ELISAs using the same capture monoclonal antibody (BC2); the second antibodies in the OSA and CASA assays are OM-1 and BC3, respectively. Using arbitrary cutoffs of 2.5 and 3.0 units/ml, 82 and 76% of 80 serum samples from ovarian cancer patients were positive for OSA and CASA, respectively, compared with 5 and 2.5% of samples from a control population of 40 women. A strong correlation was found between the two assays (r = 0.80, P less than 0.001). CA125 levels were obtained from 49 of the 80 samples; 82% of these samples were positive for CA125 (greater than 35 U/ml), 82% for OSA and 73% for CASA. Of the 9 samples negative for CA125, 3 were positive for OSA and 3 were positive for CASA. Serum OSA, CASA, and CA125 levels were determined in serial samples from 20 ovarian carcinoma patients throughout the course of their treatment. Clinical course was accurately reflected by CA125 levels in 85% of patients, by CASA in 65%, and by OSA in 75%. In 4 patients, a rise in CASA levels and, in 2 patients, a rise in OSA levels significantly predated rising CA125 levels to predict recurrence. Six of 7 serum samples obtained prior to positive second-look laparotomy were negative for CA125, while 4 were positive for OSA and 6 were positive for CASA. These results indicate that the OSA and CASA assays could be superior to CA125 for detection of small volume occult ovarian carcinoma.     

4种肿瘤标志物对上皮性卵巢癌定性诊断价值的初步研究

目的：探讨多胺（ＰＡ）、ＣＡ１２５、ＣＡ１５．３和ＣＡ１９．９在定性诊断上皮性卵巢癌中的价值。方法：应用ＨＰ％Ｍ高效液相色谱仪和ＨＰ１０４０Ａ荧光检测器或酶联免疫吸附法测定上皮性卵巢癌４０例和卵巢良性肿瘤１８例血清中ＰＡ、ＣＡ１２５、ＣＡ１５．３和ＣＡ１９．９水平。结果：４种标志物中，ＰＡ诊断卵巢癌的敏感性、阳性预测率、阴性预测率和预测准确率最高，其次是ＣＡ１２５。结论：ＰＡ对人类恶性肿瘤缺乏特异性，但可作为鉴别卵巢良、恶性病变的有价值标志物。联合测定ＰＡ和ＣＡ１２５时，其敏感率为９４．９％。因此，联合测定ＰＡ和ＣＡ１２５可作为筛查卵巢良、恶性肿瘤的方法。     

Evaluation of beta1,4-galactosyltransferase as a potential biomarker for the detection of subclinical disease after the completion of primary therapy for ovarian cancer

OBJECTIVE: Approximately 50% of patients with ovarian cancer who have normal CA 125 levels at the completion of therapy have persistent disease. In an effort to improve the ability to detect small volume disease, we have evaluated the usefulness of N-acetylglucosamine:beta1,4-galactosyltransferase as a potential biomarker for the detection of subclinical disease after the completion of primary therapy for ovarian cancer. STUDY DESIGN: The sera of 33 patients with stage IIIC epithelial ovarian cancer in complete clinical remission after chemotherapy (CA 125 <35 units/mL and negative computed tomography scan) who underwent second-look surgery were examined for N-acetylglucosamine:beta1,4-galactosyltransferase activity. The values were determined from sera that had been obtained before primary cytoreductive operation and before second-look surgery after the completion of platinum-based chemotherapy. Determinations of the levels of CA 125 were performed with the Bayer Immuno ITM CA-125 II assay. N-acetylglucosamine:beta1,4-galactosyltransferase activity was determined by measuring the transfer of galactose from uridine diphosphate- carbon 14-labeled galactose to the terminal N-acetylglucosamine residue of a very well-defined synthetic acceptor, N-acetylglucosamine:beta1,6GalNAc(alpha)-o-benzyl, which is a portion of the core structure of mucin glycoproteins. The cutoff value of N-acetylglucosamine:beta1,4-galactosyltransferase was determined to be 22,000 counts/min, based on the analysis of 25 healthy control subjects. Correlation between serum CA 125 and N-acetylglucosamine:beta1,4-galactosyltransferase levels was determined with the use of the Pearson correlation coefficient. The ability of galactosyltransferase to identify small volume disease correctly was also evaluated. RESULTS: There was a significant correlation between serum CA 125 and N -acetylglucosamine:beta1,4-galactosyltransferase levels before the operation (r = 0.57; P =.03) but not before second-look surgery (r = 0.10; P =.57). Thirteen patients (39.4%) had residual disease at second-look surgery. Elevated N-acetylglucosamine:beta-1,4galactosyltransferase activity >22,000 cpm correctly identified 10 of these patients (76.9%). The sensitivity, specificity, and positive and negative predictive values of N-acetylglucosamine:beta1,4-galactosyltransferase activity (>22,000 counts/min) for the prediction of residual disease at second-look surgery were 77%, 45%, 48%, and 77%, respectively. CONCLUSION: Our comparative study of serum CA 125 and N -acetylglucosamine:beta1,4-galactosyltransferase levels showed a significant correlation between the two tumor markers before the beginning of ovarian cancer therapy. This correlation disappeared before second-look surgery because 60% of patients with normal serum CA 125 and N-acetylglucosamine:beta1,4-galactosyltransferase levels. CA 125 antigen appears to be inferior to N -acetylglucosamine:beta1,4-galactosyltransferase in the detection of small-volume residual disease. N-acetylglucosamine:beta1,4-galactosyltransferase may be useful as a biomarker in the monitoring of patients with ovarian cancer when the serum CA 125 level is normal. These findings require confirmation in larger studies.     

Tumor markers CA 125, carcinoembryonic antigen and tumor-associated trypsin inhibitor in patients with cervical adenocarcinoma

Tumor markers CA 125, carcinoembryonic antigen (CEA) and tumor-associated trypsin inhibitor (TATI) were studied in 42 patients with cervical adenocarcinoma. Pretreatment levels of CA 125 were elevated in 73% of 33 patients, CEA in 48% of 27 patients, serum TATI in 23% of 22 patients, and urine TATI in 38% of 26 patients. Elevated CA 125 levels were associated with histological grade (P = 0.002), and elevated CEA levels with the presence of lymph node metastases (P = 0.008), respectively. No associations were found between elevated tumor marker levels and stage, or tumor size. Serum CA 125 levels increased in 71% of the patients with progressive disease, CEA levels in 36%, serum TATI levels in 46%, and urine TATI levels in 20% of the patients. In all patients with regressive disease the tumor marker levels decreased or stayed unchanged. Regression of the disease was significantly correlated (P < 0.05) with stage, histological grade, tumor size, and nodal status. The results suggest that CA 125 and, to a lesser extent, CEA and TATI are useful in the follow-up of patients with cervical adenocarcinoma.     

Serum CA 125, CA 15.3 and CA 19.9 levels and surgical findings in patients undergoing second look operations for ovarian carcinomas

Sera from 52 ovarian cancer patients undergoing chemotherapy and second look operation were studied. CA 125, CA 15.3 and CA 19.9 assays were performed during chemotherapy and prior to relaparotomy. Twenty-six patients (50%) had no evidence of disease whereas 2 (3.8%) and 24 (46.1%) had microscopic and macroscopic disease. In general although the predictive value of an elevated CA 125 or CA 15.3 level is excellent, a normal value (less than 35 U/ml) has limited significance. Moreover, we found no improvement in negative predictive and positive predictive value by adding the determination of CA 19.9.     

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

The value of CA 125 measurement in the diagnosis and follow-up of ovarian cancer was studied in 102 patients. The CA 125 levels were elevated in 88% (322/365) of samples from 82 patients with clinical evidence of disease and in 14% (56/403) of samples from 58 patients without clinical evidence. Preoperative levels were elevated in 84% (44/52) of the patients, and in 100% of those with stage III and IV disease. In patients with non-mucinous tumors the preoperative levels were elevated in 95% of cases (38/40). CA 125 levels were significantly correlated with the course of disease in 88% (36/41) of patients whose tumor regressed, and in 87% (20/23) of those whose tumor progressed. Before second-look surgery of 48 patients, the sensitivity of the CA 125 test was 35% and the specificity was 86%. The results suggest that, although far from infallible, CA 125 is a useful marker for ovarian cancer. It is useful for monitoring the course of chemotherapy, but normal levels do not rule out the possibility of persistent or recurrent disease.     

The prognostic implications of low serum CA 125 levels prior to the second-look operation for stage III and IV epithelial ovarian cancer.

Second-look laparotomy is performed to evaluate response to chemotherapy and to determine the need for additional treatment. The relationship between absolute levels of serum CA 125 less than 35 u/ml and disease status at second-look operation was evaluated in 95 patients with advanced-stage epithelial ovarian cancer. Eighty-six patients had Stage III disease and nine patients had Stage IV cancer. Residual tumor was documented at second-look laparotomy in 52 (55%) of the patients studied. Forty-nine percent of the 82 patients with serum CA 125 values less than 20 u/ml had residual disease. In contrast, 12 of 13 (92%) patients with serum CA 125 values of 20-35 u/ml had residual tumor at second-look laparotomy. All patients with serous cystadenocarcinomas and serum CA 125 values of 20-35 u/ml had residual tumor, and two-thirds of these cases had grossly visible disease. The positive predictive value of a serum CA 125 level of 20-35 u/ml was 0.92. These data suggest that second-look laparotomy should be deferred in patients with advanced-stage ovarian cancer until serum CA 125 values are less than 20 u/ml.     

Serum CA 125 as a tumor marker and the expression of c-erbB-2 oncogene in tubal malignancies

Serum CA 125 levels were evaluated in 26 patients with fallopian tube malignancies. CA 125 was elevated preoperatively in seven samples (median 178 U ml⁻¹ range 41–19021 U ml⁻¹), and postoperatively in eight of nine (89%) samples collected from patients with residual disease (median 109 U ml⁻¹ range 10–1883 U ml⁻¹) but only in one of seven (14%) samples from patients without residual disease (median 14, range 5–170 U ml⁻¹) ( P < 0.001). Changes in the serum CA 125 level during chemotherapy correlated with the clinical course of disease in 13 of 14 patients with a pre-chemotherapy serum CA 125 level> 35 U ml⁻¹. Nine patients with clinical remissions showed decreasing serum CA 125 levels, one with clinically stable disease showed decreasing levels and four with disease progression showed increasing levels. Serum CA 125 levels were measured in four patients before second-look laparotomy. Two of three with positive findings at laparotomy had elevated serum CA 125 levels whilst the third had a normal level. One patient with negative findings at second-look surgery had a normal CA 125 level. Disease relapse was associated with elevated serum CA 125 levels in nine of 10 patients (median 108 U ml⁻¹, range 27–38200 U ml⁻¹). Using immunohistochemical staining, none of the tumors showed positive cytoplasmic staining for c-erbB-2 (NEU) oncogene. This report shows that CA 125 is a reliable tumor marker for monitoring patients with cancer of the fallopian tube during active treatment and follow-up.     

Elevated CA 125 serum levels and epithelial ovarian cancer metastatic to retroperitoneal lymph nodes

Elevations in CA 125 levels have been reported in approximately 80% of patients with epithelial ovarian cancer. Studies demonstrate that elevations of CA 125 at the time of second-look procedures correlate with the presence of tumor in 100% of cases. Two cases are reported with elevated CA 125 in which clinical examination and noninvasive studies with CAT scans failed to demonstrate tumor. In both cases laparotomy was performed because of the elevation of CA 125. Although intraabdominal exploration did not reveal the source of the CA 125 elevation, extensive retroperitoneal dissection demonstrated microscopic tumor in retrocaval lymph nodes in both cases. The ability to monitor patients with CA 125 is demonstrated and the importance of elevated antigen levels emphasized. Benign conditions associated with falsely positive CA 125 are discussed.     

Use of CA 125 to monitor patients with ovarian epithelial carcinomas

The CA 125 radioimmunoassay has been increasingly used to monitor the course of patients with ovarian epithelial carcinomas. The purpose of this report is to describe our experience in the use of this assay and to better define its clinical utility. Fifty-one patients had serum CA 125 follow-up during primary chemotherapy. All 51 patients demonstrated either a normal CA 125 level at the completion of chemotherapy or a substantial fall in CA 125 values with treatment. In 48 of 51 patients, the drop in CA 125 levels was temporally related to the clinical regression or remission of tumor. Forty of these patients underwent second-look laparotomy; 23 patients (58%) had residual disease. A total of 45 patients had serum CA 125 determinations at the time of second-look laparotomy. Eight patients with microscopic disease and 11 of 18 patients with gross residual disease had a "negative" (less than 35 U/ml) CA 125 level. The predictive value of an elevated CA 125 level was 1.00. However, the predictive value of a negative value was only 0.50. Hence, a negative CA 125 level cannot be a substitute for a second-look laparotomy. Only 7 of 18 patients (39%) with gross residual disease at second-look surgery had an elevated CA 125 level. Patients with an elevated CA 125 and gross residual tumor at the second-look laparotomy uniformly demonstrated large, bulky disease. Furthermore, the survival of patients with gross residual disease at second-look laparotomy correlated with the preoperative CA 125 value. Serum CA 125 determinations also show promise in the follow-up of patients with a negative second-look laparotomy. The serum CA 125 level from patients with a "negative" second-look laparotomy can become elevated months before recurrent disease is appreciated.     

Comparison of CA 125 after three courses of chemotherapy and results of second-look surgery

OBJECTIVE: To compare CA 125 levels after three courses of cisplatin-based chemotherapy and the results of second-look surgery. METHODS AND MATERIALS: From January 1990 to December 1996, the medical records of 72 patients diagnosed with epithelial ovarian cancer were reviewed. After initial staging surgery, all patients received cisplatin-based chemotherapy. Prior to each course of chemotherapy, patients underwent physical exams and serum CA 125 was obtained. After 6 courses of chemotherapy, if CA 125 levels were normal (< or = 35 IU/ml) and there was no clinical evidence of disease, the patient was offered second-look surgery. The sensitivity, specificity, and negative predicative value of CA 125 levels after 3 courses of chemotherapy and results of second-look surgery were calculated. Survival curves were constructed using Kaplan-Meier actuarial methods. RESULTS: Seventy-two patients were enrolled in the study. After completing 3 courses of chemotherapy, 43 out of 72 patients were reported to have normal CA 125 levels and were offered second-look surgery. Forty-six out of 72 patients underwent second-look surgery, 28 patients (60%) were reported to have positive second-look surgery. Of the patients with normal CA 125 levels after 3 courses of chemotherapy, 23 patients (57.5%) had a positive second-look surgery. The sensitivity and specificity of CA 125 values after 3 courses of chemotherapy were 17.9% and 94.7%, respectively and the negative predicative value was 43.9%. Patients with normal CA 125 values after 3 courses of chemotherapy had a significantly improved survival compared to those who failed to normalized their CA 125 levels after three courses of chemotherapy. CONCLUSION: Normalization of CA 125 after 3 courses of chemotherapy is a poor predicator of findings at second-look surgery.     

CA_(125)、CA_(19.9)、CEA在卵巢上皮性交界性肿瘤中的临床价值

目的 :探讨测定血清CA12 5、CA19.9、CEA在诊断卵巢上皮性交界性肿瘤中的临床价值。方法 :回顾分析卵巢交界性肿瘤 5 0例血清CA12 5、CA19.9、CEA水平与临床资料。结果 :浆液性及粘液性肿瘤中CA12 5的阳性率分别为 5 3.85 %和 60 % ,差异无显著性 (P >0 .0 5 ) ,临床分期晚者CA12 5阳性率有增高趋势 ;粘液性肿瘤中CA19.9的阳性率为 4 3.75 % ;CEA阳性率为 12 % ,仅见于粘液性或以粘液性为主的肿瘤中 ;与术前相比 ,术后CA12 5、CA19.9水平及阳性率均显著下降 (P <0 .0 5 )。结论 :CA12 5、CA19.9对卵巢上皮性交界性肿瘤的术前诊断及疗效监测有一定价值 ,CEA则在鉴别组织学类型中有一定价值。     

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.