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

Etsuko Miyagi, Noriaki Arakawa, Kentaro Sakamaki, Naho Ruiz Yokota, Takeharu Yamanaka, Yuki Yamada, Satoshi Yamaguchi, Shoji Nagao, Yasuyuki Hirashima, Yuka Kasamatsu, Hisamori Kato, Tae Mogami, Yohei Miyagi, Hiroshi Kobayashi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1336-1344
Number of pages9
JournalInternational Journal of Clinical Oncology
Issue number7
Publication statusPublished - Jul 2021
Externally publishedYes


  • CA125
  • Clear cell carcinoma
  • Ovarian cancer
  • Serum tumor marker
  • TFPI2

ASJC Scopus subject areas

  • Surgery
  • Hematology
  • Oncology


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