| Giant cell tumors of bone (GCT) is a benign tumor according to the tradition. However, it is of high recurrence rate and occasional metastasis to the lung. Pathologically, there are newborn oval cells and consistent, large osteoclast-like giant cells. Therefore it is thought as a potential malignant tumor. Giant cell tumor accounts for 4% to 5% in the primary tumor of bone, which is about accounting 20% primary benign bone. Most patients of this disease are of 20 to 45 years old. The most common site of it is around the knee, and more in the distal femur than in the distal tibia. The most common early symptoms are pain. If there is no early diagnosis and treatment, pathologic fractures near the joints is often inevitable. Although the diagnosis, surgical techniques are in the continuous improvement, a large number of studies have shown that the composition of the cells of Giant cell tumors is complex, and the biological behavior of it varies to a large extent, leading to the Jaffe histopathological grading, Campanacci X-ray Enneking's surgical staging failing to reflect the biological behavior and clinical treatment. Therefore, there is the need to find a reliable indicator to determine the early recurrence of giant cell tumor, metastasis and prognosis.At present, the mechanism of the growth of giant cell tumor infiltration, easy to relapse and the biological behavior of the transfer start and regulatory mechanisms are still not very clear. Recent studies show that extra cell matrix, (ECM) changes in the composition of tumor invasion, recurrence is an important reason of the formation of GCT, while matrix metallo-proteinase (MMPs) is the most important a major enzyme regulate ECM homeostasis. This prompted researchers studied the matrix metallo-proteinase inhibitors in depth. Following the furthering research of the molecular biology, researchers found that many of the human matrix metallo-proteinase with the invasion is closely related with metastasis of malignant tumors [12].Matrix metalloproteinases is a kind of highly conserved zinc ion-dependent endonuclease family of proteolytic enzymes which is involved in the systemic degradation of ECM in all parts of the body. It is transferred to the secretion of plasminogen to extracellular matrix in the form of zymogen, and was activated to degrade the extracellular matrix components, destroy the natural barrier of tumor metastasis, and promote the tumor cell entering blood vessel or lymphatic. Meanwhile, it also improves the role of angiogenic factors to induce vascular generation; inhibition of tumor cell apoptosis and promote tumor proliferation and metastasis [11]. Currently, more research of giant cell tumor of bone more MMPs and their inhibitors includ MMP-1, 2,3,7,8,9,13, TIMP-2, 3 and so on. MMP-7 is one of the matrilysin, mainly expressed in normal epithelial cells, and weakly expressed or not expressed in Normal epithelial cells. Its gene is located in 1lq21-q22, and is the smallest of molecular weight in MMPs family. MMP-7 can degrade typeⅣcollagen, Gelatin, elastin, laminin and fibronectin, the important component of ECM and BM ftantetc.It can also degrade Fas ligand, thereby inhibiting Fas-mediated cell withered death, and promoting tumor growth [1]. TIMP-3 is a widely distributed endogenous inhibitor of MMPs. It is a full-functional MMP inhibitors, which has the same function of inhibition for MMP-1, 2, 9 [3].The study of the expression and regulation of MMP-7 and TIMP-3 in giant cell tumor can help to understand the MMP-7 and TIMP-3 in the giant cell tumor of bone invasion, recurrence as well as find the giant cell tumor of bone specific markers from the molecular level, leading to the improvement of the quality of the therapy and treatment of it.Method38 cases of bone giant cell tumor from March 2005 to March 2010 in the First Affiliated Hospital, the Second Hospital of surgical resection of Chongqing Medical University are taken for study, among which, there are l5 cases recurrent tumor, 23 cases of non-recurrent, and 21 male and 18 female patients aged 17 years to 57 years old (average age 35 years). The tumor tissue are embedded in paraffin with 40 g / L paraformaldehyde, buried by paraffin and cut as 4um serial sections. The expression of MMP-7, TIMP-3, CD34 in Giant cell tumors of bone and its changes in non-recurrent tumor group and the recurrent tumor group are observed by immunohistochemistry. The results of observation are tested by social statistical package SPSS17, using t test,χ2 test and spearman rank correlation analysis.Results(1) Histologic grade: According to the conventional giant cell tumor pathological grading, In this group there were 9 cases of grade I, 20 cases of gradeⅡ, 9 cases of grade.Ⅲ. (2) recurrence of tracking: l5 cases of recurrence, accounting for 39.5%, among which, the shortest time of recurrence was 4 months and the longest 28 months, with an average of 15.6 months, In another 23 tracking cases investigated from the shortest 13 months to the longest 60 months, with an average of 49.3 months, there was no recurrence. (3) Immunohistochemistry: Immunohistochemical staining showed that MMP-7 expressed in most of the multinucleated giant cells and mononuclear stromal cells isolated cytoplasm; TIMP-3 expressed in most mononuclear stromal cells and multinucleated giant cells cytoplasm and membrane. Results showed that positive rates of MMP-7 and TIMP-3 were 97% and 95%. There was significant difference (P <0. 05) between MMP-7 expression and MVD in the recurrence group and the non- recurrence group. MMP-7 positively correlated with MVD (P <0. 05); but there was no significant difference between TIMP-3 expression in the recurrence group and non-recurrent group (P> 0.05); there was no correlation significance between MMP-7 and histological grade (spearman rank correlation analysis, P> 0.05) there is no correlation among TIMP-3, MVD and histological grade (spearman rank correlation analysis, P <0. 05).Conclusion(1) MMP-7 and TIMP-3 were both highly expressed in the giant cell tumor of bone. (2) MMP-7 may accelerate tumor angiogenesis, cell proliferation and affect the recurrence of giant cell tumor of bone. (3) MMP-7 and TIMP-3 can be used as one of the reference index of the prognosis giant cell tumor of bone. |
PDF Full Text Request