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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.

The concomitant determination of different serum tumor markers in epithelial ovarian cancer: Relevance for monitoring the response to chemotherapy and follow-up of patients

The levels of CA125, CA19.9, CA15.3 CA72.4, and TATI were serially measured during and after chemotherapy in 43 patients with epithelial ovarian cancer having elevated concentrations of one or more of the antigens before initial surgery. The value of 35 U/ml was chosen as cutoff level of CA125 for the monitoring of disease. Changes in the serum levels of CA125, CA19.9, CA15.3, CA72.4, and TATI correlated with the clinical course of disease in 87.4% of 215, 76.3% of 80, 71.3% of 122, 76.0% of 167, and 48.5% of 101 instances, respectively. After the sixth course of monthly primary chemotherapy, elevated antigen levels were strong predictors of persistent disease, while normal antigen values were associated with both positive and negative second-look findings. It is worth noting that antigen levels above the cut-off limits before the third course, but still in the normal range after the sixth course, seemed to be predictive of positive second-look findings. Among patients with elevated antigen levels at diagnosis, clinical detection of neoplastic progression after treatment was stopped was preceded by an elevation of serum CA125 in 93.3% of 15 patients, of serum CA19.9 in 80.0% of 5 patients, of serum CA15.3 in 66.7% of 9 patients, of serum CA72.4 in 81.8% of 11 patients, and of serum TATI in 40% of 10 patients. In patients with positive CA125 assay at diagnosis, the concomitant evaluation of the other antigens did not seem to be of additional benefit for monitoring epithelial ovarian cancer. However, the measurement of the other tumor markers could represent an interesting biochemical tool for the management of patients with negative CA125 assay. In particular the evaluation of serum CA19.9 or CA72.4 could be very useful in the monitoring of patients with mucinous ovarian cancer, which often fails to express CA125 antigen.

Comparison of tumor-associated trypsin inhibitor (TATI) with CA125 as a marker for diagnosis and monitoring of epithelial ovarian cancer.

Preoperative serum levels of CA125 and tumor-associated trypsin inhibitor (TATI) were measured in 220 patients undergoing laparotomy for adnexal masses. Of the 57 patients with epithelial ovarian cancer. 86% had serum CA125 higher than 35 kU/l and 81% higher than 65 kU/l while 51% had serum TATI above 22 micrograms/l. In eight patients with mucinous ovarian malignancies, serum levels of CA125 were above 65 kU/l in 6 cases while serum TATI was above 22 micrograms/l in 4 cases. Of the 163 patients with benign ovarian masses, 41% had serum CA125 levels above 65 kU/l and 17% above 65 kU/l whereas serum TATI was above 22 micrograms/l in 6%. In 11 cancer patients having elevated levels of both CA125 and TATI at diagnosis, the serum concentrations of these antigens were periodically measured during and after treatment. Changes in CA125 and TATI levels correlated with the clinical course in 84% and 37% of the instances, respectively. After the sixth course of chemotherapy, the diagnostic accuracy of the markers in the evaluation of the disease status at second-look laparotomy was 55% for CA125 with a cut-off level of 35 kU/l, 36% for a cut-off level of 65 kU/l, 55% for TATI, and 66% for the combination of CA125 and TATI with cut-off levels of 65 kU/l and 22 micrograms/l. CA125 is the most sensitive marker for epithelial ovarian cancer, but the concomitant measurement of TATI could be of benefit in both differential diagnosis of adnexal masses and monitoring of response of epithelial ovarian cancer to treatment.