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Reduced expression of tissue factor pathway inhibitor-2 contributes to apoptosis and angiogenesis in cervical cancer

Qiao Zhang1, Yao Zhang1, Shi Z Wang1, Ning Wang1, Wei G Jiang2, Yao H Ji3 and Shu L Zhang1*

Author Affiliations

1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang(110004), China

2 Department of Pathology, Shengjing Hospital of China Medical University, Shenyang (110004), China

3 Virus Laboratory, Shengjing Hospital of China Medical University, Shenyang (110004), China

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Journal of Experimental & Clinical Cancer Research 2012, 31:1 doi:10.1186/1756-9966-31-1

Published: 2 January 2012

Abstract

Background

Tissue factor pathway inhibitor-2 (TFPI-2) is an extracellular matrix associated broad-spectrum Kunitz-type serine proteinase inhibitor. Recently, down regulation of TFPI-2 was suggested to be involved in tumor invasion and metastasis in some cancers.

Methods

This study involved 12 normal cervical squamous epithelia, 48 cervical intraepithelial neoplasia (CIN), and 68 cervical cancer. The expression of TFPI-2, Ki-67 and vascular endothelial growth factor (VEGF) were investigated by immunohistochemistry staining. The apoptolic index(AI) was determined with an in situ end-labeling assay(TUNEL). And the marker of CD34 staining was used as an indicator of microvessel density (MVD).

Results

TFPI-2 expression has a decreasing trend with the progression of cervical cancer and was significantly correlated with FIGO stage, lymph node metastasis and HPV infection. In addition, there were significant positive correlations between the grading of TFPI-2 expression and AI(P = 0.004). In contrast, the expression of TFPI-2 and VEGF or MVD was negatively correlated (both p < 0.001). However, we did not establish any significant correlation between Ki-67 and TFPI-2 expression in cervical cancer.

Conclusions

The results suggested that the expression of TFPI-2 had a decreasing trend with tumor progression of cervical cancer. There was a close association between the expression of TFPI-2 and tumor cell apoptosis and angiogenesis in patients with cervical cancer. TFPI-2 may play an inhibitive role during the development of cervical cancer.

Keywords:
cervical cancer; Tissue factor pathway inhibitor-2; immunohistochemical study; apoptosis; angiogenesis