Expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in malignant peripheral nerve sheath tumor

Abstract

Background Matrix metalloproteinase-9 (MMP-9) can degrade collagen IV (the main structural ingredient of basilar membrane), and it also plays an important role in tumor vascularization, tumor cell progression, formation of metastatic focus, etc. Tissue inhibitor of metalloproteinase-1 (TIMP-1) can bind with MMP-9 to form 1:1 compound and inhibit its activity, and can negatively regulate the tumor progression and metastasis. Objective To analyze the relationship of MMP-9 and TIMP-1 expressions with the pathological grade, metastasis and prognosis of malignant peripheral nerve sheath tumor (MPNST). Design An observational comparative experiment. Setting Heze Medical College. Participants Fifty-eight surgical pathological samples, which were clearly diagnosed to be MPNST, were collected from the pathological laboratory archives in the Department of Pathology, Heze Municipal Hospital from January 1988 to December 2003. The MPNST pathological types were common tumor in 53 cases, malignant triton tumor in 2 cases, epithelial MPNST in 2 cases and MPNST with gland differentiation in 1 case. The pathological grade was grade 1 in 11 cases, grade 2 in 24 cases and grade 3 in 23 cases. Besides, the resected tumor samples of 20 patients with benign peripheral nerve tumor (10 cases of nerve sheath tumor and 10 cases of neurofibromatosis) and the normal peripheral nerves (by-products of some surgeries) of 5 patients were also collected. The samples were used with the approval of the patients. Rat-anti-human MMP-9, TIMP-1 monoclonal antibody and S-P kit were purchased from Fuzhou Maixin Biotechnology, Co., Ltd. Methods The documented paraffin blocks were again prepared to sections of 5 μm. The expressions of MMP-9 and TIMP-1 in the samples were detected with mmunohistochemical S-P method. The relationships of the MPNST severity, recurrence, metastasis and survival rate with the expressions of MMP-9 and TIMP-1 were analyzed. Main outcome measures Relationships of MMP-9 and TIMP-1 expressions with the MPNST severity and prognosis. Results ▪ Expressions of MMP-9 and TIMP-1 in three tissues: MMP-9 and TIMP-1 stainings were mainly observed in cytoplasm. Among the 58 MPNST patients, the MMP-9 expression was significantly higher than those in normal peripheral nerve and benign tumor ( P < 0.05), while the TIMP-1 expression in MPNST was lower than those in normal peripheral nerve and benign tumor ( P < 0.05). ▪ Relationship of MMP-9 and TIMP-1 expressions with the severity and prognosis of MPNST: The expressions of both proteins were observed in the four subtypes. The positive expression of MMP-9 in the MPNST patients of grades 2–3 was significantly higher than that in the MPNST patients of grade 1 ( P < 0.05), while the expression of MMP-9 was significantly lower than that in the MPNST patients of grade 1 ( P < 0.05). The metastatic rate was positively correlated with MMP-9 expression ( r = 1.696, P < 0.05), but negatively correlated with TIMP-1 expression ( r = –2.125, P < 0.05). Conclusion MMP-9 and TIMP-1 are associated with MPNST pathological grades and metastasis, and can be used as the indicators for judging the severity and prognosis of MPNST.