Circulating DF3 and CA125 antigen levels in serum from patients with epithelial ovarian carcinoma.

The murine monoclonal antibody (MAb), designated DF3, reacts with a 300-kilodalton (kd) mammary epithelial antigen. A sequential double-determinant enzyme-linked immunoassay (EIA) has been developed to monitor circulating DF3 antigen. Previous studies have demonstrated that the use of the DF3 EIA provides a new and potentially useful marker to follow the clinical course of patients with metastatic breast cancer. In the present study, we have monitored circulating DF3 antigen in the serum of patients with epithelial ovarian carcinomas and non-ovarian gynecologic malignancies. Twenty-one of 45 patients (47%) with ovarian carcinoma had elevated DF3 antigen levels (greater than or equal to 30 U/mL). In contrast, three of 20 patients (15%) with non-ovarian gynecologic malignancies, and only four of 59 control women (7%) had elevation of circulating DF3 antigen. The difference between DF3 antigen values from patients with ovarian cancer and from controls was significant (P less than .001). The elevation of circulating DF3 antigen in ovarian cancer patients has also been confirmed by transblot assays. MAb DF3 reactivity occurred predominately with circulating antigens of molecular weights (mol wt) ranging from 300 to 450 kd. Furthermore, DF3 antigen levels have been shown to correlate with progression of disease in six patients with ovarian cancer and after resection of disease in two others. The half-life of circulating DF3 antigen was approximately 45 to 60 days. The results also demonstrate that DF3 antigen is distinct from CA125, a glycoprotein associated with coelomic epithelium and developmental amnion. The use of both the DF3 EIA and the immunoradiometric assay previously described to detect circulating CA125 suggests that determining levels of both markers may enhance the sensitivity of monitoring the course of ovarian cancer. Furthermore, the use of both assays may be useful in distinguishing ovarian cancer from other malignancies.

Recombinant leukocyte alpha interferon in advanced ovarian carcinoma.

Recombinant leukocyte alpha interferon (rIFN-alpha A; Hoffmann-La Roche, Inc) was administered to 15 patients with recurrent or persistent ovarian carcinoma. All patients had been previously treated with surgery and combination chemotherapy including cyclophosphamide (15 patients), doxorubicin (14), and cisplatin (14). Three patient had also previously undergone radiation therapy. At the start of therapy the largest tumor size was less than or equal to 2 cm in four patients and greater than 2 cm in 11. Interferon was administered in three times weekly for 8 weeks at a dose of 20 X 10(6) units/m2, with average drug levels of 2267 pg/ml 6 hours after im injection. In three patients (20%), the dose had to be reduced by 50% because of drug toxicity. Side effects included fever (greater than 101 degrees F) in 12 patients, fatigue in ten, headache in two, diarrhea in two, and reversible myelosuppression in five. Of the 15 patients, one had mixed response lasting 12 weeks, two had stable disease of 8 weeks' duration, and 12 had disease progression.

Predictive value of CA 125 antigen levels in second-look procedures for ovarian cancer.

Serum CA 125 levels were evaluated in 44 patients undergoing 56 second-look or subsequent laparoscopies (43) and laparotomies (13) for ovarian cancer. In each patient studied, a previous CA 125 level had been greater than or equal to 35 U/ml. Clinical or radiologic evidence of tumor was absent in all patients at the time of surgical evaluation. CA 125 levels were less than 35 U/ml in 36 cases (64%); 14 patients were free of tumor, while 22 were found to have tumor at surgery. CA 125 levels were greater than or equal to 35 U/ml in 20 cases; 18 had tumor at surgery, one has had recurrence of tumor, and the other remains clinically free of tumor at 3 months. A CA 125 level less than 35 U/ml was not predictive of the presence of intraperitoneal tumor; however, when tumor was present in this group of patients, the largest tumor mass did not exceed 1 cm. In contrast, a CA 125 level greater than or equal to 35 U/ml was a strong predictor of the presence of intraperitoneal tumor or future recurrence. These data suggest that second-look procedures may not be required in the select group of patients with CA 125 levels greater than or equal to 35 U/ml.

CA125 antigen levels in obstetric and gynecologic patients.

An immunoradiometric assay using a monoclonal antibody detects an antigenic determinant (CA125) that is present in more than 80% of epithelial ovarian cancers. CA125 levels are elevated in the sera of 16% of women in the first trimester of pregnancy and is found in very high concentration in amniotic fluid. In 988 nonpregnant patients with benign gynecologic disorders, CA125 was greater than 65 U/mL in 1% on a single determination and in 0.5% with two determinations. Given the low rate of positivity in benign gynecologic disease, the CA125 assay may deserve further evaluation for the early detection of ovarian carcinoma.

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.

Elevation of serum CA125 in carcinomas of the fallopian tube, endometrium, and endocervix.

An immunoradiometric assay with the use of a monoclonal antibody can detect an antigenic determinant (CA125) in peripheral blood from more than 80% of patients with epithelial ovarian cancer. In this report elevated levels of CA125 were detected in serum from patients with adenocarcinomas of the fallopian tube, endometrium, and endocervix. Among patients with endometrial cancer, CA125 levels were elevated in recurrent or disseminated disease but not with tumors confined to the uterus.