Detecting chromosomal alterations at 1p and 19q by FISH and DNA fragment analysis – a comparative study in human gliomas

Broholm, Helle; Pw, Born; Guterbaum, D; Dyrbye, Henrik; Laursen, Henning

doi:10.5414/npp27378

Cited by 16 publications

(9 citation statements)

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“…In summary, the commercially purchased probes used for hybridization were Zytolight SPEC 1p36/1q25 and 19q13/19p13 dual color probes (Nordic BioSite, Sweden). Slides were assessed under a fluorescence microscope (Olympus BX 50 Deutschland GmbH) and a minimum of 100 non-overlapping nuclei was counted per hybridization [ 11 ]. A tumor was considered deleted if >50% of the nuclei harbored two signals of the reference probe, but only one signal of the target probe.…”

Section: Methodsmentioning

confidence: 99%

Prognostic markers for survival in patients with oligodendroglial tumors; a single-institution review of 214 cases

et al. 2017

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BackgroundIn the 2016 WHO classification, the diagnosis of oligodendroglioma has been restricted to IDH mutated, 1p19q codeleted tumors (IDHmut-codel). IDHmut oligoastrocytoma is now classified either as oligodendroglioma or astrocytoma based on presence of 1p19q codeletion. There is growing evidence that this molecular classification more closely reflects patient outcome. Due to the strong association between IDHmut-codel with oligodendroglial morphology, the additional impact of these markers on prognostic accuracy is largely unknown. Our aim was to assess the prognostic impact of IDHmut-codel in an unselected cohort of morphologically classified oligodendroglial tumors.MethodsWe performed a retrospective chart review of oligodendroglial tumors (WHO grade II and III) operated since 1983. A total of 214 tumors were included, and molecular information was available for 96 tumors. The prognostic impact of IDHmut-codel together with clinical parameters was analyzed by multivariate Cox regression.ResultsIDHmut-codel was registered in 64 tumors while for 150 tumors the molecular profile was negative for IDHmut-codel, unknown or incomplete. Comparison between the two groups showed that patients with IDHmut-codel tumors were younger (42 vs. 48 years), had more frequent frontal tumor location (48 vs. 33%) and presented more often with seizures (72 vs. 51%) and no signs of neurological impairment (14 vs. 30%) than patients harboring tumors with unknown or incomplete molecular profile. Multivariate survival analysis identified young age (HR 1.78 ≥ 40 years), the absence of neurological deficits or personality changes (HR 0.57), frontal tumor location (HR 0.64) and the presence of IDHmut-codel (HR 0.50) as independent predictors for longer survival, whereas tumor grade was not.ConclusionIn this unselected single-institution cohort, the presence of IDHmut-codel was associated with more beneficial clinical parameters and was identified as an independent prognostic factor. We conclude that the classical oligodendroglioma genotype provides additional prognostic data beyond clinical characteristics, morphology and tumor grade.

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Section: Methodsmentioning

confidence: 99%

Prognostic markers for survival in patients with oligodendroglial tumors; a single-institution review of 214 cases

et al. 2017

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“…Fluorescent in situ hybridisation analysis (FISH) on paraffin sections to study losses of the chromosomal arms 1p and 19q was performed as described previously (Broholm et al , 2008). The commercially purchased probes used for hybridisation were Zytolight SPEC 1p36/1q25 and 19q13/19p13 dual colour probes (Nordic BioSite, Täby, Sweden).…”

Section: Methodsmentioning

confidence: 99%

PROX1 is a predictor of survival for gliomas WHO grade II

Elsir

Berntsson

et al. 2011

Br J Cancer

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Background:The clinical course of World Health Organisation grade II gliomas remains variable and their time point of transformation into a more malignant phenotype is unpredictable. Identification of biological markers that can predict prognosis in individual patients is of great clinical value. PROX1 is a transcription factor that has a critical role in the development of various organs. PROX1 has been ascribed both oncogenic and tumour suppressive functions in human cancers. We have recently shown that PROX1 may act as a diagnostic marker for high-grade gliomas. The aim of this study was to address the prognostic value of PROX1 in grade II gliomas.Methods:A total of 116 samples were evaluated for the presence of PROX1 protein. The number of immunopositive cells was used as a variable in survival analysis, together with established prognostic factors for this patient group.Results:Higher PROX1 protein was associated with poor outcome. In the multivariate analysis, PROX1 was identified as an independent factor for survival (P=0.024), together with the presence of mutated isocitrate dehydrogenase 1 R132H protein, and with combined losses of chromosomal arms 1p/19q in oligodendrocytic tumours.Conclusion:PROX1 is a novel predictor of survival for grade II gliomas.

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“…FISH has been shown a reliable method for the analysis of the 1p 19q status in oligodendroglial tumors [17]. In addition, several independent studies found good concordance between FISH and PCR-based LOH or MLPA results [11,13,22,41]. However, inter-observer and inter-laboratory variability have not yet been addressed in a systematic way, and common standards for 1p 19q FISH procedures across neuropathology laboratories are still lacking.…”

Section: Analytical Performance Of Fish-based 1p 19q Testingmentioning

confidence: 99%

FISH-based detection of 1p 19q codeletion in oligodendroglial tumors: procedures and protocols for neuropathological practice – a publication under the auspices of the Research Committee of the European Confederation of Neuropathological Societies (

Wöehrer

Sander²,

Haberler³

et al. 2011

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The codeletion of chromosomal arms 1p 19q is a characteristic and early genetic event in oligodendroglial tumors, that is associated with a better prognosis and enhanced response to therapy. Over the last years, the increasing clinical demand to determine the 1p 19q status has led to the implementation of its testing in many neuropathology laboratories. Several different methods for 1p 19q testing are available: PCR-based loss of heterozygosity analysis, multiplex ligationdependent probe amplification, array comparative genomic hybridization, and fluorescence in situ hybridization (FISH). Herein, we focus and critically discuss the latter method because a detailed description of procedures and protocols for FISH-based 1p 19q testing in practice is lacking. We present a practical approach to the FISH-based assessment of the 1p 19q status in oligodendroglial tumors, from commonly used locus-specific probes and technical protocols to the neuropathological interpretation of results. Thereby, we aim to facilitate the implementation of FISH-based 1p 19q testing for clinical purposes in standard neuropathology laboratories without special focus on brain tumor research.

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Detecting chromosomal alterations at 1p and 19q by FISH and DNA fragment analysis – a comparative study in human gliomas

Cited by 16 publications

References 0 publications

Prognostic markers for survival in patients with oligodendroglial tumors; a single-institution review of 214 cases

Prognostic markers for survival in patients with oligodendroglial tumors; a single-institution review of 214 cases

PROX1 is a predictor of survival for gliomas WHO grade II

FISH-based detection of 1p 19q codeletion in oligodendroglial tumors: procedures and protocols for neuropathological practice – a publication under the auspices of the Research Committee of the European Confederation of Neuropathological Societies (

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