A Clinical Prognostic Analysis Of Gliosarcoma And Preliminary Study Of MGMT And IDH1Expressions In Gliosarcoma And Their Correlations With The Prognosis

Objectives:Gliosarcoma is a rare type of central nervous system neoplasm, which is considered as a variant type of glioblastoma. Literatures focusing on gliosarocma are limited. MGMT is a very important prognostic molecule in the treatment of malignant glioma. IDH1mutation has been proved to exist in low grade glioma and secondary GBM, using as a prognostic factor of glioma. However, the research of MGMT and IDH1expressions in gliosarcoma is still limited. This retrospective study demonstrates the clinical, imaging and pathological features of primary and secondary gliosarcoma respectively, and analyzes the prognostic factors of gliosarcoma. This study is designed to examine the expressions of MGMT, IDH1and other molecular markers in gliosarcoma and explore their correlation with the prognosis.Meterials and methods:We retrospectively discuss the clinical characteristics and pathological features of gliosarcoma that have been diagnosed between2002and2010in Huashan Hospital. We analyze the factors affecting the survival curve based on univariate analysis using Kaplan-Meier survival analysis, and analyze independent prognostic factors using Cox proportional hazards regression analysis. We use H&E staining and immunohistochemical staning to detect the expression of MGMT, IDH1, p53, CD34and Ki67in gliosarcoma respectively, and analyze the correlation between the expression of MGMT, IDH1, Ki67and the prognosis of gliosarcoma.Results:36patients meet the demand in this study, including28primary gliosarcoma and8secondary gliosarcoma.61.1%patients are male while38.9%are female. The median age of gliosarcoma is50.5years old, with the preference in the location of temporal lobe (41.7%).4cases (11.1%) are suffered from multiple intracranial lesions. The median Karnofsky performance scale is80. All these36patients underwent craniotomies, with gross total resection in32patients (88.9%).22patients (61.1%) received post operative radiotherapy while17patients (47.2%) received chemotherapy.According to the pre-operative image and macro appearance during the operation, we find the gliosarcoma have heterogeneity which can be categorized in three groups, GBM-like group, cystic solid-lesion group and meningioma-like group.The median OS of these groups are12months,5months and12months respectively, without a significant difference in survival (p=0.649).PGS has a6-month survival rate of71.1%,1-year survival rate of46.4%,2-year survival rate of27.5%and median OS of12months. SGS has a6-month survival rate of37.5%and median OS of6months. On univariate analysis, we found PGS has longer OS than SGS (12months vs6months, p=0.003). Patients with one intracranial lesion have longer OS than those with multiple intracranial lesions (10months vs5months, p<0.019). Patients with totol resection of the tumor have longer OS than those with subtotal or partial resection of the tumor (10months vs5months, p=0.04). Patients who received post-operative radiotherapy have longer OS than those who didn’t (13months vs5months, p<0.001). Patients who received post-operative chemotherapy have longer OS than those who didn’t (17months vs6months, p=0.004). On multivariate analysis, post-operative radiotherapy is an independent prognostic factor of gliosarcoma with a hazard ratio of4.160. We then describe the clinical manifestations and pathological features of8secondary gliosarcoma patients and analyze the prognosis and experience in the treatment.We use immunohistochemical staining to detect the expression of MGMT, IDH1, Ki67, CD34, p53in gliosarcoma. MGMT expression was found positive in8patients with an positve rate of22.2%. The median OS and PFS of the MGMT-negative patients are9months and6months respectively, compared to8months and4months in the MGMT-positive patients. However, log rank test shows no significant difference in median OS (p=0.952) and PFS (p=0.473) between the two groups. IDH1were found negative in all the gliosarcoma but posive in the control case.We use Kaplan-Meier survival curve to analyze the correlation between the expression of Ki67and the prognosis. The median OS of Ki67-group, Ki67+group, Ki67++group and Ki67+++group are respectively8months,8months,8months and 9months, with no differences among these groups (p=0.784). The median PFS of each group are5months,4months,5months and6months, with no differences among these groups as well (p=0.754).p53expression was found positive in14patients, with an expression rate of38.9%.88.9%patients were found identical p53expression in the glial component and the sarcomatous component. CD34was positive in the non-endovascular epithelial cells in7patients, with an expression rate of19.4%, and it was found positive in both glial and sarcomatous areas. In5patients of recurrent or metastatic specimen, there’s no significant difference in the expression of MGMT, p53, Ki67or CD34compared to those of primary tumors. Furthermore, no significant difference was detected between SGS and corresponding primary glioma in the expression of MGMT, p53, K167or CD34.Conclusions:Gliosarcoma have the preference of male in the age from30years old to60years old, with temporal lobe as the most common location. But no specific imaging features of gliosarcoma are found in this study. Gliosarcoma have a tendency of intracranial spread and extracranial metastases.SGS have worse prognosis than PGS. Post-operative radiotherapy is an independent prognostic factor of gliosarcoma. Lesion number, extent of resection and post-operative chemotherapy may have correlations with the prognosis of gliosarcoma, which need more cases to demonstrate.MGMT expression can be detected in gliosarcoma using immunohistochemical staining. But IDH1mutation was found in neither PGS nor SGS. Expression of MGMT and Ki67does not have correlation with prognosis of gliosarcoma.