Upregulated matrix metalloproteinase-2 and downregulated tissue factor pathway inhibitor-2 are risk factors for lymph node metastasis and perineural invasion in pancreatic carcinoma

Abstract

Background: Dysregulated expression of matrix metalloproteinase (MMP)-2 and tissue factor pathway inhibitor (TFPI)-2 is closely associated with tumorigenesis and tumor progression. The aim of this work was to determine the predictive values of MMP-2 and TFPI-2 in identifying lymph node metastasis (LNM) and perineural invasion (PNI) in pancreatic carcinoma. Methods: Formalin-fixed and paraffin-embedded tissue samples containing pancreatic carcinoma tissues and their corresponding para-carcinoma tissues were obtained from 122 patients with pancreatic carcinoma. The expression levels of MMP-2 and TFPI-2 were evaluated by immunohistochemistry. The roles of MMP-2 and TFPI-2 in predicting LNM and PNI in pancreatic carcinoma were analyzed. Results: The level of MMP-2 expression was markedly increased in pancreatic carcinoma tissues (76.9%) compared with para-carcinoma tissues (29.2%; P<0.05). In contrast, there was obviously decreased TFPI-2 expression level in pancreatic carcinoma tissues (29.2%) compared with para-carcinoma tissues (77.7%; P<0.001). Additionally, MMP-2 expression was significantly positively correlated with LNM (r=0.468, P<0.01) and PNI (r=0.637, P<0.01). In contrast, TFPI-2 expression was strongly negatively correlated with LNM (r=-0.396, P<0.001) and PNI (r=-0.460, P<0.001). Logistic regression analysis showed that high MMP-2 expression and low TFPI-2 expression acted as independent predictors for LNM and PNI in pancreatic carcinoma. Conclusion: Taken together, our findings suggest that upregulated MMP-2 and downregulated TFPI-2 serve as useful predictors for a high risk of LNM and PNI. Obtaining information on the expression of MMP-2 and TFPI-2 before surgery may predict the occurrence of LNM and PNI, thereby permitting reasonable and effective surgical treatment for patients with pancreatic carcinoma.