The tissue factor pathway inhibitor-2 (TFPI2) was recently identified as a diagnostic serum marker for ovarian clear cell carcinoma. Moreover, the immunohistochemical expression of TFPI2 in ovarian clear cell carcinoma was recently reported. This single-center retrospective study aimed to evaluate whether TFPI2 can be a specific biomarker for immunohistological diagnosis of endometrial clear cell carcinoma (ECCC). Immunohistochemical staining of TFPI2 in 55 endometrial carcinomas was evaluated at Nara Medical University Hospital. Thirteen ECCC samples were included as cases and 42 samples were included as a control (endometrioid carcinoma grade 1, 11 cases; grade 2, 11 cases; grade 3, 10 cases; serous carcinoma, 10 cases). The mean ± SD TFPI2 histoscore for diagnosing ECCC was 115.4 ± 87.9, which was significantly higher than that of non-ECCC (21.3 ± 45.9, P = 0.002). The best TFPI2 histoscore value obtained from the analyses of receiver operating characteristic curves for immunohistochemical diagnosis of ECCC was 15. With TFPI2 histoscores ≥15.0 as positive and <15.0 as negative, all 13 ECCC cases (100%) were positive for TFPI2, whereas 11 (26.2%) non-ECCC cases were positive for TFPI2. The sensitivity and specificity of TFPI2 for diagnosing ECCC were 100% and 73.8%, respectively. TFPI2 is expressed in ECCC and is useful for histopathological diagnosis.

01 Sep 2021·Journal of Obstetrics and Gynaecology ResearchQ4 · MEDICINE

Toward an understanding of tissue factor pathway inhibitor‐2 as a novel serodiagnostic marker for clear cell carcinoma of the ovary

Q4 · MEDICINE

Review

Author: Kobayashi, Hiroshi ; Imanaka, Shogo

AbstractAimsTissue factor pathway inhibitor (TFPI)‐2 has recently emerged as a serodiagnostic marker for patients with epithelial ovarian cancer (EOC), especially clear cell carcinoma (CCC). This review discusses the biological properties of TFPI‐2 and why serum levels are elevated in CCC patients.MethodsA comprehensive literature search was conducted in PubMed up until March, 2021.ResultsTFPI‐2 is a Kunitz‐type protease inhibitor and negatively regulates the enzymatic activities, such as plasmin. TFPI‐2 has been characterized as a tumor suppressor gene and was frequently downregulated through promoter hypermethylation in various human cancers. In contrast, TFPI‐2 was overexpressed only in CCC. TFPI‐2 may be involved in the pathophysiology of CCC, possibly through regulation of coagulation system, stabilization of extracellular matrix (ECM), and induction of intracellular signal transduction. TFPI‐2 suppresses tissue factor‐induced hypercoagulation in a hypoxic environment. TFPI‐2, secreted by CCC cells, platelets, and adjacent vascular endothelial cells, may suppress tumor growth and invasion through ECM remodeling. Nuclear TFPI‐2 may suppress matrix metalloproteinase production via transcription factors and modulate caspase‐mediated cell apoptosis. CCC cells may upregulate the TFPI‐2 expression to adapt to survival in the demanding environment. TFPI‐2 is secreted by CCC cells and enters the systemic circulation, resulting in elevated blood levels.DiscussionSerum TFPI‐2 reflects the overexpression of TFPI‐2 in CCC tissues and is a potential serodiagnostic marker. Further research is needed to explore the expression, clinical significance, biological function, and potential mechanism of TFPI‐2 in CCC.

01 Aug 2014·European Archives of Oto-Rhino-LaryngologyQ3 · MEDICINE

The role of tissue factor pathway inhibitor-2 in malignant transformation of sinonasal inverted papilloma

Q3 · MEDICINE

Article

Author: Huan Wang ; Li Hu ; Juan Liu ; Xicai Sun ; Quan Liu ; Dehui Wang ; Huapeng Yu

The aim was to evaluate the potential role of tissue factor pathway inhibitor-2 (TFPI-2) in the process of malignant transformation of sinonasal inverted papilloma (SIP). We evaluated the expression of TFPI-2 in 23 SIP and 8 SIP with squamous cell carcinoma (IPcSCC), compared to 9 normal sinonasal mucosa by means of Western blot and immunohistochemistry staining. In addition, angiogenesis, vascular endothelial growth factor (VEGF) expression and microvessel density marked by CD105 staining were assessed. Correlation of TFPI-2 expression and angiogenesis in the process of malignant transformation of SIP was investigated. Western blot results demonstrated that the protein level of TFPI-2 in IPcSCC was significantly lower than that in the control group (P < 0.01). In addition, significant difference in TFPI-2 protein expression between SIP and IPcSCC was detected (P < 0.01). Higher number of microvessel per unit area (MVNA) was observed in IPcSCC compared to SIP (P < 0.01). Correlational analysis indicated positive correlation of VEGF and MVNA (r = 0.735), inverse correlation of TFPI-2 and MVNA (r = -0.318). However, no significant correlation between TFPI-2 and VEGF was detected. We conclude that TFPI-2 might be a regulatory molecule in the malignant potential of SIP. Down regulation of TFPI-2 is associated with increased MVNA in IPcSCC, which may be involved in the process of malignant transformation of SIP.

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