Abstract
BackgroundTissue 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.MethodsThis 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).ResultsTFPI-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.ConclusionsThe 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.
Highlights
Tissue factor pathway inhibitor-2 (TFPI-2) is an extracellular matrix associated broad-spectrum Kunitztype serine proteinase inhibitor
We studied the correlation between TFPI-2 and apoptosis, ki-67, vascular endothelial growth factor (VEGF) and microvessel density (MVD) expression to evaluate whether TFPI-2 contributed to tumor cell apoptosis, proliferation and angiogenesis in patients with cervical cancer
All normal squamous epithelial cells showed potent immunostaining for cytoplasmic TFPI-2 (Figure 2A), while the staining for cytoplasmic TFPI-2 was lower in ICC (Figure 2D)
Summary
Tissue factor pathway inhibitor-2 (TFPI-2) is an extracellular matrix associated broad-spectrum Kunitztype serine proteinase inhibitor. Down regulation of TFPI-2 was suggested to be involved in tumor invasion and metastasis in some cancers. TFPI-2 gene is located on chromosome 7q22, and consists of three Kunitz-type serine proteinase inhibitory domains similar to the classical tissue factor pathway inhibitor (TFPI-1). It is reported that upregulation the expression of MMPs strongly associated with the progression of several malignancies, including cervical cancer [8]. TFPI-2 has been reported to effectively regulate MMPs activity by inhibiting activation of proMMPs by trypsinlike serine proteinases [9]. Recent findings suggest decreasing TFPI-2 expression plays a significant role in inhibiting cell migration and tumor invasion by a mechanism that involves its inhibitory activity [11,12]. The expression of TFPI-2 has not yet been examined in cervical tissues
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