The Expression and Significance of MGMT, Ku80 and Ki67 Gene in Different Grades of Spinal gliomas
Compared to cranial gliomas, the spinal cord glioma is a rare tumor of the central nervous system. Due to its infrequent incidence, there is no consensus regarding the management of spinal cord glioma until nowadays. Radical surgery, radiation therapy, and chemotherapy have been used in various combinations around the world; so far the extent of resection and the use of adjuvant chemotherapy or radiotherapy have not been clearly shown to be associated with a survival advantage. MGMT is one of the most important genetic factors determining drug resistance while Ku80 determining radiosensitivity, and Ki67 determining tumor proliferation. The expression of MGMT, Ku80 and Ki67 in spinal glioma remains unclear. If they interfere with the chemosensitivity, radiosensitivity and with the prognosis of spinal glioma, an optimized therapeutic protocol might be found based on these molecular factors. The aim of our study was to detect the expression of MGMT, Ku80 and Ki67 on spinal glioma by immunohistochemistry staining and to assess the relationship between MGMT and Ki67, and Ku80 and Ki67 expression level and clinical outcomes, thus determine whether these immunophenotypes were prognostic factors in spinal glioma. At the same time we evaluated the efficacy of surgery, radiotherapy and chemotherapy efficacy in a series of spinal gliomas through the retrospective analysis. 65 patients with spinal glioma from Germany and China were included in this retrospective study. All tissues were reviewed and diagnosed with H.E staining by a neuropathologist. The expression of MGMT, Ku80 and Ki67 in tumor samples was determined by immunohistochemistry using the MGMT, Ku80 and Ki67 monoclonal mouse antihuman antibody. One thousand neoplastic cells per specimen were counted. On the basis of the percentages of positive cells in the tumors, these tumors were defined as low MGMT expression or low Ku80 expression when there were fewer than 50% positive cells, and high expression when positive rate was more than 50%. A low Ki67 expression was defined as less than 10% positive cells and a high expression when the positive rate was more than 10%. Analyses were performed with the use of SPSS 17.0. The mean expression level of MGMT, Ku80 and Ki67 in 65 spinal gliomas was 44.6%±33.6%, 59.0%±29.3% and 7.2%±11.7%. resp. A correlation was found between MGMT and Ki67 proteins expressions (r=-0.242, P=0.052). A significant difference in MGMT expression could be found between age<50 years old group and age≥50 years old group (P=0.05). Differences in Ku80 and MGMT expression between primary and recurrent spinal gliomas did not reach significance (P>0.05). Kaplan-Meier analysis revealed that patients with tumors showing a high Ki67 expression had significantly shorter progress free survival (PFS) than patients who had low Ki67 expression (122.3 months vs. 43.8 months; P =0.010). Expression of Ki67, extent of resection, radiotherapy, chemotherapy were related with prognosis in spinal glioma (P<0.05), whereas MGMT and Ku80 expression were not statistically significant, but showed to be potentially related to tumor recurrence and metastases formation (MGMT (P=0.065) and Ku80 (P=0.088)). This study showed that the expression of MGMT, Ku80 and Ki67 could be observed in the majority of spinal gliomas. It is the first time to detect the expression of MGMT, Ku80 and Ki67 proteins in spinal glioma with immunohistochemistry staining method , Ki67 even predicting survival in this study. In addition to,Ki67 and other clinical variables including tumor location, extent of resection, radiotherapy, chemotherapy are correlated significantly with OS and PFS.