Abstract:
Objective To investigate the clinical significance of tissue factor pathway inhibitor-2 (TFPI-2) and its role in the prognosis of gastric cancer. This study also aims to analyze the correlation among TFPI-2, endothelium-dependent angiogenesis, and vasculogenic mimicry (VM) in gastric cancer.
Methods Immunohistochemic staining was conducted to detect the expression of TFPI-2 protein and analyze its relationship with clinicopathological parameters from 187 gastric cancer cases. The microvessel density was measured through CD34 immunohistochemistry stain, and the distribution feature of VM was observed via CD34/periodic acid-schiff double staining.
Results The positive expression rate of TFPI-2 was approximately 48.1% (90 / 187). The expression of the TFPI-2 protein was correlated with the tumor differentiation degree, tumor node metastasis stage, lymph node metastasis, invasion, and distant metastasis. However, it was not correlated with gender, age, tumor location, tumor maximal size, and clinical stage. The Kaplan-Meier survival analysis showed that patients with the higher expression of TFPI-2 had longer overall survival time and disease-free survival time than those with lower expression of TFPI-2. The relationship between TFPI-2 and tumor angiogenesis mode showed that TFPI-2 was negatively correlated with endotheli um-dependent angiogenesis. No correlation was found between TFPI-2 and VM in all samples of gastric cancer. In well-differentiated gastric cancer, TFPI-2 was negatively correlated with endothelium-dependent angiogenesis. TFPI-2 expression was not correlated with VM but was positively correlated with VM in poorly-differentiated gastric cancer.
Conclusion TFPI-2 expression decreased with the development of tumor malignancy degree and exhibited a significant effect on the prognosis of gastric cancer. In addition, TFPI-2 expression was closely correlated with endothelium-dependent angiogenesis. It inhibited invasion and metastasis, thus suppressing the progress of well differentiated gastric cancer. Moreover, TFPI-2 promoted the formation of vasculogenic mimicry in highly malignant and poorly differentiated gastric cancer. TFPI-2 may be a dual function regulator for angiogenesis mode in gastric cancer.