Nuclear karyopherin a2: a novel biomarker for infiltrative astrocytomas

The karyopherin (KPNA) protein family is involved in nucleocytoplasmic trafficking. Increased KPNA levels have been found to predict poor prognosis for a variety of solid tumors, including breast, ovarian, cervical, and prostate cancer, and melanoma. The purpose of this study was to evaluate karyopherin a2 as novel biomarker for astrocytic gliomas of WHO grades II-IV. We semiquantitatively measured nuclear expression of karyopherin a2 and the MIB1 labeling index, by immunohistochemical analysis, for 94 primary (23 astrocytomas WHO grade II, 24 astrocytomas WHO grade III, 47 glioblastomas) and 12 recurrent gliomas. In addition, IDH1 mutation status and Nijmegen breakage syndrome 1 protein expression were assessed, by immunohistochemical analysis, for all 71 malignant (WHO grade III and IV) and all 94 primary gliomas, respectively. Statistical analysis was performed by use of standard techniques. Karyopherin a2 expression correlated significantly with histological grade (p < 0.001), with proliferative activity as assessed by the MIB1 index (p < 0.001), with IDH1 mutation status (p = 0.032), and with Nijmegen breakage syndrome 1 protein expression (p = 0.001). Recurrent tumors expressed significantly higher levels of karyopherin a2 (p = 0.045) than primary growths. Multivariate analysis of the overall series identified low karyopherin a2 expression (defined as less than 5 %) as an independent prognostic predictor of overall (p = 0.041) and progression-free survival (p = 0.004). Survival of glioblastoma patients >5 years was seen only in those with KPNA2 expression levels ≤1 % (p = 0.014). KPNA2 expression may have potential as a novel diagnostic and prognostic biomarker for astrocytic gliomas.