TY  - JOUR
A1  - Linsenmann, Thomas
A1  - Monoranu, Camelia M.
A1  - Alkonyi, Balint
A1  - Westermaier, Thomas
A1  - Hagemann, Carsten
A1  - Kessler, Almuth F.
A1  - Ernestus, Ralf-Ingo
A1  - Löhr, Mario
T1  - Cerebellar liponeurocytoma - molecular signature of a rare entity and the importance of an accurate diagnosis
JF  - Interdisciplinary Neurosurgery
N2  - Background:
Cerebellar liponeurocytoma is an extremely rare tumour entity of the central nervous system. It is histologically characterised by prominent neuronal/neurocytic differentiation with focal lipidisation and corresponding histologically to WHO grade II. It typically develops in adults, and usually shows a low proliferative potential. Recurrences have been reported in almost 50% of cases, and in some cases the recurrent tumour may display increased mitotic activity and proliferation index, vascular proliferations and necrosis. Thus pathological diagnosis of liponeurocytoma is challenging. This case presentation highlights the main clinical, radiographic and pathological features of a cerebellar liponeurocytoma.

Case presentation:
A 59-year-old, right-handed woman presented at our department with a short history of persistent headache, vertigo and gait disturbances. Examination at presentation revealed that the patient was awake, alert and fully oriented. The cranial nerve status was normal. Uncertainties were noted in the bilateral finger-to-nose testing with bradydiadochokinesis on both sides. Strength was full and no pronator drift was observed. Sensation was intact. No signs of pyramidal tract dysfunction were detected. Her gait appeared insecure. The patient underwent surgical resection. Afterward no further disturbances could be detected.

Conclusions:
To date >40 cases of liponeurocytoma have been reported, including cases with supratentorial location. A review of the 5 published cases of recurrent cerebellar. Liponeurocytoma revealed that the median interval between the first and second relapse was rather short, indicating uncertain malignant potential. The most recent WHO classification of brain tumours (2016) classifies the cerebellar liponeurocytoma as a separate entity and assigns the tumour to WHO grade II. Medulloblastoma is the most important differential diagnosis commonly seen in children and young adults. In contrast, cerebellar liponeurocytoma is typically diagnosed in adults. The importance of accurate diagnosis should not be underestimated especially in the view of possible further therapeutic interventions and for the determination of the patient's prognosis.
KW  - liponeurocytoma
KW  - neurocytoma
KW  - medulloblastoma
KW  - molecular signature
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177652
VL  - 16
ER  - 
TY  - JOUR
A1  - Feldheim, Jonas
A1  - Kessler, Almuth F
A1  - Schmitt, Dominik
A1  - Wilczek, Lara
A1  - Linsenmann, Thomas
A1  - Dahlmann, Mathias
A1  - Monoranu, Camelia M
A1  - Ernestus, Ralf-Ingo
A1  - Hagemann, Carsten
A1  - Löhr, Mario
T1  - Expression of activating transcription factor 5 (ATF5) is increased in astrocytomas of different WHO grades and correlates with survival of glioblastoma patients
JF  - OncoTargets and Therapy
N2  - Background: 
ATF5 suppresses differentiation of neuroprogenitor cells and is overexpressed in glioblastoma (GBM). A reduction of its expression leads to apoptotic GBM cell death. Data on ATF5 expression in astrocytoma WHO grade II (low-grade astrocytoma [LGA]) are scarce and lacking on recurrent GBM.

Patients and methods: 
ATF5 mRNA was extracted from frozen samples of patients’ GBM (n=79), LGA (n=40), and normal brain (NB, n=10), quantified by duplex qPCR and correlated with retrospectively collected clinical data. ATF5 protein expression was evaluated by measuring staining intensity on immunohistochemistry.

Results: 
ATF5 mRNA was overexpressed in LGA (sevenfold, P<0.001) and GBM (tenfold, P<0.001) compared to NB, which was confirmed on protein level. Although ATF5 mRNA expression in GBM showed a considerable fluctuation range, groups of varying biological behavior, that is, local/multifocal growth or primary tumor/relapse and the tumor localization at diagnosis, were not significantly different. ATF5 mRNA correlated with the patients’ age (r=0.339, P=0.028) and inversely with Ki67-staining (r=-0.421, P=0.007). GBM patients were allocated to a low and a high ATF5 expression group by the median ATF5 overexpression compared to NB. Kaplan–Meier analysis and Cox regression indicated that ATF5 mRNA expression significantly correlated with short-term survival (t<12 months, median survival 18 vs 13 months, P=0.022, HR 2.827) and progression-free survival (PFS) (12 vs 6 months, P=0.024). This advantage vanished after 24 months (P=0.084).

Conclusion: 
ATF5 mRNA expression could be identified as an additional, though not independent factor correlating with overall survival and PFS. Since its inhibition might lead to the selective death of glioma cells, it might serve as a potential ubiquitous therapeutic target in astrocytic tumors.
KW  - glioblastoma multiforme
KW  - recurrence
KW  - growth pattern
KW  - protein and mRNA expression
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177541
VL  - 11
ER  -