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Preoperative serum neopterin, soluble interleukin-2 receptor (sIL-2R), and CA125 levels were assayed in 47 patients with ovarian cancer and 113 patients with benign ovarian disease undergoing laparotomy. The cutoff limits of the antigens for the preoperative evaluation of ovarian cancer were fixed according to the Youden plot, using the patients with benign ovarian disease as controls. These limits were 7.9 nmole/liter for neopterin, 71 U/ml for sIL-2R, and 83 U/ml for CA125. The preoperative mean values of serum neopterin and sIL-2R were significantly higher in patients with ovarian cancer than in those with benign ovarian disease. Therefore these tests would seem to be useful in distinguishing benign from malignant ovarian masses. Serum levels of neopterin, sIL-2R, and CA125 above the cutoff limits were detected in 66.0, 78.7, and 76.6% of patients with ovarian cancer. Patients with advanced-stage disease (FIGO > or = III) were significantly more likely to have a higher percentage of elevated values of sIL-2R and CA125, but not neopterin, compared to patients with early-stage disease. However, neopterin was the antigen most often raised in early disease. As for advanced ovarian cancer, preoperative serum sIL-2R levels were higher in patients who developed progressive disease than in those who were progression-free (P = 0.02) after a median follow-up time of 18 months. Furthermore, a trend to higher preoperative serum neopterin values was found in the former patients (P = 0.08). Tumor progression occurred in 3 of 8 (37.5%) patients with low serum preoperative neopterin (< 7.9 nmole/liter) and in 16 of 19 (84.2%) patients with elevated serum neopterin, respectively (P = 0.027). Multivariate analysis on a larger number of patients followed for a longer time is warranted to elucidate the prognostic relevance of these immunologic markers in ovarian cancer. Changes in serum neopterin, sIL-2R, and CA125 levels correlated with the disease course in 50.0, 54.8, and 92.9% of 42 instances, respectively. Moreover, serum CA125 was more sensitive than the other two antigens in the early detection of tumor progression. Therefore serial neopterin and sIL-2R measurements seem to be of limited value in monitoring the disease course in patients with ovarian cancer.