Clinical characteristics and pathogenesis of cerebellar glioblastoma

Takahashi,Yoshinobu; Makino,Keishi; Nakamura,Hideo; Hide,Takuichiro; Yano,Shigetoshi; Kamada,Hajime; Kuratsu,Jun-Ichi

doi:10.3892/mmr.2014.2549

Clinical characteristics and pathogenesis of cerebellar glioblastoma

Authors:
- Yoshinobu Takahashi
- Keishi Makino
- Hideo Nakamura
- Takuichiro Hide
- Shigetoshi Yano
- Hajime Kamada
- Jun-Ichi Kuratsu
View Affiliations

Affiliations: Department of Neurosurgery, Graduate School of Medical Science, Kumamoto University, Kumamoto 860-8556, Japan, Department of Neurosurgery, Hokuto Hospital, Obihiro, Hokkaido 080-0039, Japan
Published online on: September 9, 2014 https://doi.org/10.3892/mmr.2014.2549
Pages: 2383-2388

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Cerebellar glioblastomas (GBMs) are rare, with neither their pathogenesis nor prognosis being completely understood. The present study aimed to clarify the clinical characteristics of cerebellar GBMs by comparison with supratentorial GBMs, focusing particularly on the pathogenesis. The clinical factors between cerebellar (n=10) and supratentorial (n=216) GBMs were compared. Additionally, p53 and epidermal growth factor receptor (EGFR) levels were investigated in six patients by immunostaining as well as the isocitrate dehydrogenase 1 (IDH1) status of five patients by direct sequencing. Eight males and two females participated in the present study, the mean age at diagnosis was 56.6 years and the range 37-75 years. Four patients presented with hydrocephalus and one with brainstem involvement, and two patients were diagnosed with neurofibromatosis type 1. Two patients had previously received radiotherapy, eight patients received postoperative radiotherapy and seven chemotherapy. The mean Karnofsky performance status (KPS) score was lower in patients with cerebellar GBMs compared to those with supratentorial GBM; however, the survival times did not differ between the two groups. All of the cases of six cerebellar GBMs were p53‑positive and EGFR‑negative, as detected by immunostaining, consistent with secondary GBM. However, no IDH1 mutations were detected in any of the five cases of cerebellar GBMs analyzed, indicating that these tumors were not of the secondary type. The KPS score with cerebellar GBMs may be lower due to hydrocephalus, which was ameliorated by surgery but may have impacted the survival rate. It was confirmed that cerebellar GBMs were identical to supratentorial GBMs with respect to its clinical features, with the possible exception of the KPS score. The present study's genetic analyses indicated that cerebellar GBMs may develop via a pathway different from that of either primary or secondary GBM.

View Figures

View References

1	Roth JG and Elvidge AR: Glioblastoma multiforme: a clinical survey. J Neurosurg. 17:736–750. 1960. View Article : Google Scholar : PubMed/NCBI
2	Grahovac G, Tomac D, Lambasa S, et al: Cerebellar glioblastomas: pathophysiology, clinical presentation and management. Acta Neurochir (Wien). 151:653–657. 2009. View Article : Google Scholar : PubMed/NCBI
3	Salazar OM: Primary malignant cerebellar astrocytomas in children: a signal for postoperative craniospinal irradiation. Int J Radiat Oncol Biol Phys. 7:1661–1665. 1981. View Article : Google Scholar
4	Kleihues P and Ohgaki H: Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro-Oncol. 1:44–51. 1999.PubMed/NCBI
5	Ohgaki H and Kleihues P: Genetic pathways to primary and secondary glioblastoma. Am J Pathol. 170:1445–1453. 2007. View Article : Google Scholar : PubMed/NCBI
6	Nobusawa S, Watanabe T, Kleihues P, et al: IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res. 15:6002–6007. 2009. View Article : Google Scholar : PubMed/NCBI
7	Weber DC, Miller RC, Villà S, et al: Outcome and prognostic factors in cerebellar glioblastoma multiforme in adults: a retrospective study from the rare cancer network. Int J Radiat Oncol Biol Phys. 66:179–186. 2006. View Article : Google Scholar : PubMed/NCBI
8	Tsung AJ, Prabhu SS, Lei X, Chern JJ, Benjamin Bekele N and Shonka NA: Cerebellar glioblastoma: a retrospective review of 21 patients at a single institution. J Neurooncol. 105:555–562. 2011. View Article : Google Scholar : PubMed/NCBI
9	Lammert M, Friedman JM, Kluwe L, et al: Prevalance of neurofibromatosis 1 in German children at elementary school enrollment. Arch Dermatol. 141:71–74. 2005. View Article : Google Scholar : PubMed/NCBI
10	Easton DF, Ponder SM, Huson SM, et al: An analysis of variation in expression of neurofibromatosis (NF) type 1 (NF1): evidence for modifying genes. Am J Hum Genet. 53:305–313. 1993.PubMed/NCBI
11	Brown PD, Buckner JC, O’Fallon JR, et al: Adult patients with supratentorial pilocytic astrocytomas: a prospective multicenter clinical trial. Int J Radiat Oncol Biol Phys. 58:1153–1160. 2004. View Article : Google Scholar : PubMed/NCBI
12	Canesso A, Gardiman M, Salmaso R, et al: An unusual case of malignant pilocytic astrocytoma occurring in the eye. Virchows Arch. 449:248–252. 2006. View Article : Google Scholar : PubMed/NCBI
13	Gilles FH, Sobel EL, Tavaré CJ, et al: Age-related changes in diagnoses, histological features, and survival in children with brain tumors: 1930–1979. The Childhood Brain Tumor Consortium. Neurosurgery. 37:1056–1068. 1995.PubMed/NCBI
14	Roessler K, Bertalanffy A, Jezan H, et al: Proliferative activity as measured by MIB-1 labeling index and long-term outcome of cerebellar juvenile pilocytic astrocytomas. J Neurooncol. 58:141–146. 2002. View Article : Google Scholar
15	Cawthon RM, Weiss R, Xu GF, et al: A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell. 62:193–201. 1990. View Article : Google Scholar : PubMed/NCBI
16	Xu GF, Lin B, Tanaka K, et al: The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants of S.cerevisiae. Cell. 63:835–841. 1990. View Article : Google Scholar : PubMed/NCBI
17	Zhu Y, Guignard F, Zhao D, et al: Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma. Cancer Cell. 8:119–130. 2005. View Article : Google Scholar : PubMed/NCBI
18	Klériga E, Sher JH, Nallainathan SK, et al: Development of cerebellar malignant astrocytoma at site of a medulloblastoma treated 11 years earlier. Case report. J Neurosurg. 49:445–449. 1978.PubMed/NCBI
19	Cohen MS, Kushner MJ and Dell S: Frontal lobe astrocytoma following radiotherapy for medulloblastoma. Neurology. 31:616–619. 1981. View Article : Google Scholar : PubMed/NCBI
20	Furuta T, Sugiu K, Tamiya T, et al: Malignant cerebellar astrocytoma developing 15 years after radiation therapy for a medulloblastoma. Clin Neurol Neurosurg. 100:56–59. 1998.PubMed/NCBI
21	Nakamizo A, Nishio S, Inamura T, et al: Evolution of malignant cerebellar astrocytoma at the site of a treated medulloblastoma: report of two cases. Acta Neurochir (Wien). 143:697–700. 2001. View Article : Google Scholar : PubMed/NCBI
22	Osumi AK, Mclendon RE, Tien RD, et al: Well differentiated astrocytoma occurring nine years after radiation therapy for medulloblastoma. Clin Neuropathol. 13:281–285. 1994.PubMed/NCBI
23	Pearl GS, Mirra SS and Miles ML: Glioblastoma multiforme occurring 13 years after treatment of a medulloblastoma. Neurosurgery. 6:546–551. 1980.PubMed/NCBI
24	Safneck JR, Napier LB and Halliday WC: Malignant astrocytoma of the optic nerve in a child. Can J Neurol Sci. 19:498–503. 1992.
25	Schmidbauer M, Budka H, Bruckner R, et al: Glioblastoma developing at the site of a cerebellar medulloblastoma treated 6 years earlier. Case report. J Neurosurg. 67:915–918. 1987.PubMed/NCBI
26	Paulino AC, Mai WY, Chintagumpala M, et al: Radiation-induced malignant gliomas: is there a role for reirradiation? Int J Radiat Oncol Biol Phys. 71:1381–1387. 2008. View Article : Google Scholar : PubMed/NCBI
27	Utsuki S, Oka H, Miyajima Y, et al: Adult cerebellar glioblastoma cases have different characteristics from supratentorial glioblastoma. Brain Tumor Pathol. 29:87–95. 2012. View Article : Google Scholar
28	Saito T, Hama S, Kajiwara Y, et al: Prognosis of cerebellar glioblastomas: correlation between prognosis and immunoreactivity for epidermal growth factor receptor compared with supratentorial glioblastomas. Anticancer Res. 26:1351–1357. 2006.
29	Akimoto J, Fukami S, Tsutsumi M, et al: Radiopathological characteristics of cerebellar malignant glioma in adults. Brain Tumor Pathol. 26:59–68. 2009. View Article : Google Scholar : PubMed/NCBI
30	Balss J, Meyer J, Mueller W, et al: Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol. 116:597–602. 2008. View Article : Google Scholar : PubMed/NCBI
31	Gravendeel LA, Kloosterhof NK, Bralten LB, et al: Segregation of non-p.R132H mutations in IDH1 in distinct molecular subtypes of glioma. Hum Mutat. 31:E1186–E1190. 2010. View Article : Google Scholar : PubMed/NCBI
32	Ichimura K, Pearson DM, Kocialkowski S, et al: IDH1 mutations are present in the majority of common adult gliomas but are rare in primary glioblastomas. Neuro Oncol. 11:341–347. 2009. View Article : Google Scholar : PubMed/NCBI
33	Sanson M, Marie Y, Paris S, et al: Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol. 27:4150–4154. 2009. View Article : Google Scholar : PubMed/NCBI
34	Sonoda Y, Kumabe T, Nakamura T, et al: Analysis of IDH1 and IDH2 mutations in Japanese glioma patients. Cancer Sci. 100:1996–1998. 2009. View Article : Google Scholar : PubMed/NCBI
35	van den Bent MJ, Dubbink HJ, Marie Y, et al: IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Clin Cancer Res. 16:1597–1604. 2010.
36	Watanabe T, Nobusawa S, Kleihues P, et al: IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol. 174:1149–1153. 2009. View Article : Google Scholar : PubMed/NCBI
37	Weller M, Felsberg J, Hartmann C, et al: Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the German Glioma Network. J Clin Oncol. 27:5743–5750. 2009. View Article : Google Scholar