The Expression of MGMT and Ku80 in Primary Central Nervous System Lymphoma and Prognostic Significance
|Institution:||Christian-Albrechts-Universität zu Kiel|
|Full text PDF:||http://macau.uni-kiel.de/receive/dissertation_diss_00016574|
The primary central nervous system lymphoma (PCSNL), as one of the uncommon extranodal lymphomas, has been recently paid more attention especially for its increasing incidence, unsatisfactory therapy and poor prognosis. MGMT is one of the most important factors determining drug resistance while Ku80 determining radiosensitivity, the expression of MGMT and Ku80 in PCNSL remains unclear. The aim of our study was to detect the expression of MGMT and Ku80 on PCNSL by IHC staining and to evaluate the relationship between Ku80, MGMT expression level and clinical outcomes, thus determine whether these immunophenotypes were prognostic factors in PCNSL. 49 patients with PCNSL were included in this retrospective study. The expression of Ku80 and MGMT in tumor samples was determined by immunohistochemistry using the Ku80 and MGMT 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 Ku80 expression or low MGMT expression when there are no or fewer than 50% positive cells, and high expression when positive rate was more than 50%. The expression levels were than compared to the clinical data and statistical analyzed. The mean expression level of Ku80 and MGMT in 49 PCNSL were 64.1±24.5 and 51.3±29.5 respectively. A correlation was found between these two proteins expressions (r=0.311, P=0.029). A significant difference in Ku80 expression could be found between age<65 years group and age≥65 years group (P=0.006), Differences in Ku80 and MGMT expression between primary and secondary CNS lymphomas did not reach significance (P>0.05). Kaplan-Meier analysis revealed that patients who showed a high Ku80 expression had a significantly shorter median survival time (MST) than patients who had low Ku80 expression (55.3 months vs. 80.4 months; P =0.036). This could not be observed for the MGMT expression. Patients’ age, tumor location, treatment protocol, alkylating agents were significantly related with prognosis in PCNSL (P<0.05). The results of this study show that the expression of Ku80 and MGMT can be found in the majority of PCNSLs, although without statistically difference compared with their expressions in secondary CNS lymphoma. It is the first time to detect the expression of Ku80 proteins in PCNSL. Ku80 expression was a positive predictor for survival in this study. Immunohistochemical detection of MGMT does not correlate with overall survival, and cannot be used as a prognostic factor. With Ku80 we can add another predictor to evaluate the prognosis in patients with PCSNL and confirm the relevance of patient age and tumor location at the time of diagnosis in the prognosis of PCSNL.