gms | German Medical Science

Objective: The family of karyopherins comprises importins and exportins which are both involved in nucleocytoplasmic shuttling. Increased levels of karyopherin a2/importin 1 (KPNA2) and chromosome region maintenance protein 1/exportin 1 (CRM1) have been associated with poorer prognosis in patients with infiltrative astrocytomas.

Method: We evaluated KPNA2 and CRM1, as well as the IDH1 mutation status as possible novel biomarkers also for anaplastic oligoastrocytomas (AOA) WHO grade III. We analyzed nuclear expression of KPNA2 by immunohistochemistry in 72 primary anaplastic gliomas (29 AOA: 24 anaplastic astrocytomas (AA): 19 anaplastic oligodendrogliomas (AO)). The IDH1 mutation status was also determined by patients with AA and AOA, whereas the latter patients were additionally evaluated for CRM1 nuclear expression.

Results: Long-term survivors with AOA (LTS: Overall Survival >8 yrs.) showed lower KPNA2 expression levels compared to non-LTS (p=0.005). KPNA2 expression (≥5% vs. <5%, 1–5% median) were found to correlate inversely with overall survival (OS) and progression-free survival (PFS) in our overall series as well as in the group of AOA (anaplastic gliomas: OS, p=0.017, PFS, p=0.033; AOA: OS, p=0.017, PFS, p=0.040). Mutant IDH1-R132H was detected in 69% of our cohort with AOA; a combination of KPNA2 low expression and mutant IDH1-R132H was only seen in LTS (p=0.050). No differences between the histological subtypes were observed in terms of KPNA2 expression and IDH1-R132H mutation status.

Conclusions: For the first time we could show that KPNA2 expression may have potential as prognostic biomarker for AOA as well.