Validation of tissue factor pathway inhibitor 2 as a specific biomarker for preoperative prediction of clear cell carcinoma of the ovary

Abstract

Background Tissue factor pathway inhibitor 2 (TFPI2) is a novel serum biomarker that discriminates ovarian clear cell carcinoma (CCC) from borderline ovarian tumors (BOTs) and non-clear cell epithelial ovarian cancers (EOCs). Here, we examined the performance of TFPI2 for preoperative diagnosis of CCC. Methods Serum samples were obtained preoperatively from patients with ovarian masses, who needed surgical treatment at five hospitals in Japan. The diagnostic powers of TFPI2 and cancer antigen 125 (CA125) serum levels to discriminate CCC from BOTs, other EOCs, and benign lesions were compared. Results A total of 351 patients including 69 CCCs were analyzed. Serum TFPI2 levels were significantly higher in CCC patients (mean ± SD, 508.2 ± 812.0 pg/mL) than in patients with benign lesions (154.7 ± 46.5), BOTs (181 ± 95.5) and other EOCs (265.4 ± 289.1). TFPI2 had a high diagnostic specificity for CCC (79.5%). In patients with benign ovarian endometriosis, no patient was positive for TFPI2, but 71.4% (15/21) were CA125 positive. TFPI2 showed good performance in discriminating stage II–IV CCC from BOTs and other EOCs (AUC 0.815 for TFPI2 versus 0.505 for CA125) or endometriosis (AUC 0.957 for TFPI2 versus 0.748 for CA125). The diagnostic sensitivity of TFPI2 to discriminate CCC from BOTs and other EOCs was improved from 43.5 to 71.0% when combined with CA125. Conclusions High specificity of TFPI2 for preoperative detection of CCC was verified with the defined cutoff level of TFPI2 in clinical practice. TFPI2 and CA125 may contribute substantially to precise prediction of intractable CCC.

Tissue factor pathway inhibitor 2: A potential diagnostic marker for discriminating benign from malignant ovarian tumors

“…To our knowledge, this is the first study to evaluate the clinical usefulness of TFPI2 alone and in combination with multiple markers and algorithms in discriminating between benign and malignant ovarian tumors. First, our results are in agreement with Miyagi et al 14 and Arakawa et al, 12,13 who found that TFPI2 enhances diagnostic accuracy for OC because its expression pattern is unaffected by the menstrual cycle phase and endometriosis (Figures 1 and S1). We demonstrated for the first time that serum TFPI2 levels did not largely differ by the histological type of OC (Figure 2).…”

“…Previous clinical studies demonstrated that TFPI2 has a high specificity for CCC (79.5%) and is often negative in women with endometriosis. 13,14 Therefore, TFPI2 has been expected as a serodiagnostic marker to complement CA125 testing. 13,14 However, it remains unclear whether TFPI2 can more accurately distinguish benign from malignant ovarian tumors when compared to the conventional markers or algorithms with higher diagnostic performance.…”

Tissue Factor Pathway Inhibitor 2: A Novel Biomarker for Predicting Asymptomatic Venous Thromboembolism in Patients with Epithelial Ovarian Cancer

“…TFPI2 is a secreted Kunitz-type protease inhibitor and has inhibitory activities against the tissue factor (TF) blood coagulation pathway, factor Xa, plasmin, plasma kallikrein, trypsin, and chymotrypsin [9]. Since April 2021, the TFPI2 test has been covered by the Japanese national health insurance system as a serodiagnostic marker for ovarian cancer [8, 10, 11]. Recently, serum TFPI2 levels are elevated in VTE patients [12].…”

Tissue factor pathway inhibitor 2 as a serum marker for diagnosing asymptomatic venous thromboembolism in patients with epithelial ovarian cancer and positive D‑dimer results

“…TFPI2 is a novel serodiagnostic marker for EOC (14-16). TFPI2 levels were significantly increased in patients with CCC than those without CCC, suggesting that TFPI2 may help diagnose CCC (14)(15)(16). The TFPI2 test has been covered by the Japanese national health insurance system since April 2021.…”

“…Several studies have demonstrated that TFPI1 downregulation is a valuable clinical predictor of deep vein thrombosis (DVT) (8)(9)(10)(11)(12)(13). Recently, TFPI2 has been verified as a novel serum marker for diagnosing EOC, especially CCC (14)(15)(16). However, no study has focused on TFPI2 as a marker for clinically diagnosing VTE in various cancers, including EOC.…”