Tissue factor pathway inhibitor II as a specific biomarker for pre-operative prediction of clear-cell carcinoma of the ovary.

Abstract

e18077 Background: Tissue factor pathway inhibitor 2 (TFPI2) is a novel serum biomarker that discriminates ovarian clear cell carcinomas (CCC) from borderline ovarian tumors (BD) and non-CCC epithelial ovarian cancers (EOC). We examined the prediction performances of TFPI2, including high specificity, for preoperative diagnosis of CCC in multi-center settings. Methods: We collected serum samples obtained preoperatively from patients with ovarian masses who needed surgical treatment to confirm pathological diagnoses in five hospitals in Japan. The diagnostic powers of serum levels of TFPI2 (cutoff value 270 pg/mL) and CA125 (cutoff value 35 U/mL) to discriminate CCC from BD, non-CCC-EOC, and benign lesions were compared. Results: A total of 351 patients (77 ovarian benign lesions, 65 BD and 209 EOC including 69 CCC) 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), BD (181±95.5) and non-CCC EOC (265.4±289.1). TFPI2 had a high diagnostic specificity to CCC (sensitivity and specificity: 43.5% and 79.5%, respectively). The sensitivity of TFPI2 was improved to 71.1% when combined with CA125, and it was increased in Stage II–IV CCC (66.7%) compared with Stage I CCC (33.3%). In patients with benign endometriotic cysts (BEM), 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 BD and non-CCC EOC patients (AUC 0.815 for TFPI2 versus 0.505 for CA125) or from BEM (AUC 0.957 for TFPI2 versus 0.748 for CA125). Conclusions: High specificity of TFPI2 for the preoperative detection of CCC was re-verified with the defined cutoff level of TFPI2 in practice. TFPI2 and CA125 may have a substantial contribution to the precise prediction of intractable CCC. [Table: see text]