S_ary In ovarian cancer patients a 6 kDa polypeptide, the tumour-associated trypsin inhibitor (TATI), can occur at elevated concentrations in both unrne and serum. In this study pretreatment serum levels of TATI (cut-off point 21 ngml-') and CA 125 (cut-off points 35Uml-' and 65Uml-') were determined in 152 patients with epithelial ovarian cancer (115 primary and 37 recurrent) and in 267 women with benign pelvic diseases. The data obtained were correlated with the tumour stage, histological type and tumour grade. Overall, TATI showed a sensitivity of 64% and a specificity of 75%. The sensitivity and specificity of CA 125 > 35 U ml-' were both 80%. Corresponding values for CA 125 > 65 U ml-' were 70% and 87%. The combination of the two markers increased the sensitivity to 91% (CA 125> 35 U ml-') and 86% (CA 125 > 65 U ml-'), while the specificity dropped to 61% and 68% respectively. TATI was clearly superior in mucinous carcinomas of the ovary, the rate of true-positive findings in these neoplasms was 67% vs 42% for CA 125 > 35 U ml-' and 33% for CA 125 > 65 U ml-'. Unlike With a sensitivity of more than 80%, the tumour marker CA 125 plays a major role in the detection and follow-up of ovarian cancer. In patients with malignant ovarian neoplasms another potential marker can, however, occur at elevated concentrations in both urine and serum: a 6 kDa polypeptide, the tumour-associated trypsin inhibitor TATI. Its structure is identical to that of PSTI, the pancreatic secretory trypsin inhibitor, which protects the pancreas from autodigestion Huhtala et al., 1982Huhtala et al., , 1983. As TATI suppresses both the tumour-associated isoenzymes TAT-1 and TAT-2 which may promote tumour invasion by activating prourokinase, it inhibits tissue destruction by trypsin (Koivunen et al., 1989) and is thus an indicator of the proteolytic activity of the tumour.While high TATI levels are present in the cyst fluid of both benign and malignant mucinous ovarian cysts, concentrations in serous fluids are elevated only in the presence of carcinoma. However, concentrations found in the cyst fluid do not correlate with the serum levels (Hahila et al., 1987).Elevated TATI levels have also been shown to be present in 90% of all pancreatic carcinomas and in 60-70% of gastrointestinal carcinomas (Haglund et al., 1986;Tomita et al., 1990). In malignant ovarian neoplasms, TATI mainly appears to be useful for detecting mucinous carcinomas (Mogensen et al., 1990a, Torre et al., 1991.The purpose of this study was to determine whether TATI provides information other than that provided by CA 125 when used as a marker for epithelial carcinoma of the ovary.
Materials and metodBetween May 1988 and June 1993 serum levels of CA 125 and TATI were determined before laparotomy in 419 consecutive patients with epithelial carcinoma of the ovary (n = 152) or benign pelvic disease (n = 267). The patients were between 23 and 87 years of age (mean age 62.4 years). As surgery is known to induce elevated serum levels, samples obtained within the first 4 weeks p...