Expression of Matrix Metalloproteinase 2 and Extracellular Matrix Metalloproteinase Inducer are Unfavorable Postoperative Prognostic Factors in Intrahepatic Cholangiocarcinoma

Many investigators have indicated that overexpression and amplification of matrix metalloproteinase 2 (MMP-2) and extracellular matrix metalloproteinase inducer (EMMPRIN) are independent prognostic factors for primary tumors. We studied expression of them in tissues from intrahepatic cholangiocarcinoma (IHCCA) and normal bile ducts, and discussed the occurrence and development of IHCCA. Another goal was to explore possible association of MMP-2 and EMMPRIN with clinicopathologic parameters and prognosis of IHCCA. MMP-2 and EMMPRIN expression in 106 cases of IHCCA tissues and 15 cases of normal bile ducts were examined by immunohistochemical staining. Then, the association of MMP-2 and EMMPRIN expression with clinicopathologic parameters and patients' prognosis was analyzed. The positive expression levels of MMP-2 and EMMPRIN associated significantly with various clinicopathologic risk factors, such as poor histologic differentiation (p=0.03, 0.02), higher TNM stages (p=0.02, 0.01) and decreased tumor-specific survival. In particular, the tumor-specific survival rate of the patients with MMP-2+/EMMPRIN+expression was the lowest (p<0.01). Using Cox regression analysis of the 89 patients, the conjoined expressions of MMP-2-/EMMPRIN-, MMP-2+/EMMPRIN +, histologic differentiation, and the clinical TNM stages of tumorous tissues were independent prognostic indicators of IHCCA (p<0.01, p<0.01, p=0.02, p=0.01 and p=0.01, respectively). MMP-2 and EMMPRIN expression in primary tumor predicts an unfavorable prognosis in IHCCA, suggesting a crucial role of the two markers in progression of human IHCCA.