Hayashi T, Hayakawa Y, Koh M, Tomita T, Nagai S, Kashiwazaki D, Sugimori M, Origasa H, Kuroda S:
Impact of a novel marker, T-LAK cell originating protein kinase (TOPK) expression on outcome in malignant glioma. Neuropathology 21 DEC 2017 | DOI: 10.1111/neup.12446

Abstract
This study was aimed to evaluate the biological features of T-LAK cell originating protein kinase (TOPK) in vitro and to assess clinical impact of TOPK on the outcome in the patients with malignant glioma. TOPK protein level and TOPK mRNA level in six glioma-cell lines were examined using Western blot and RT-PCR, respectively. Immunohistochemistry was performed to examine their subcellular localization of TOPK. Using surgical specimen from 57 patients with gliomas, TOPK and Ki-67 expressions were examined by immunohistochemistry. Their co-localization was also examined with double fluorescence immunohistochemistry. Impacts of TOPK/Ki-67 expression on the overall survival (OS) and progression-free survival (PFS) in 32 patients with glioblastoma multiforme (GBM) were examined, using Kaplan-Meier and Cox proportion hazard model. Immunohistochemistry revealed that approximately 20 to 30% of glioma cells were positive for TOPK in vitro. TOPK mRNA was identified in all glioma cell lines on RT-PCR. The value of TOPK/GAPDH was 0.27±0.11. TOPK and Ki-67 expressions were significantly higher in GBM patients than in non-GBM patients. A majority of TOPK-positive cells were also positive for Ki-67 and vice versa. Multivariate analysis revealed that a low TOPK expression (≤12.7%) was an independent predictor of longer OS (P=0.0372), and that gross total removal and a low TOPK expression (≤12.7%) were independent predictors of longer PFS (P=0.0470 and P=0.0189, respectively). The findings strongly suggest biological and clinical importance of TOPK expression in gliomas, indicating a novel therapeutic potential of TOPK inhibitors to treat malignant gliomas.