Benes, Ludwig

Bertalanffy, Helmut

Bozinov, Oliver

Köhler, Sylvia

Miller, Dorothea

Ritter, Markus

Samans, Birgit

Sure, Ulrich

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ERRATUMCandidate genes for the progression of malignantgliomas identified by microarray analysisNegative results in the logarithmic M AstroIII/GBM quotient represents upregulationof the geneOliver Bozinov & Sylvia Köhler & Birgit Samans &Ludwig Benes & Dorothea Miller & Markus Ritter &Ulrich Sure & Helmut BertalanffyPublished online: 27 February 2008# Springer-Verlag 2008Erratum to: Neurosurg Rev (2008) 31:83-90DOI 10.1007/s10143-007-0107-3It was brought to our attention, that there is a misinterpre-tation of the data in the text of our article [2]. After com-paring our data with the original ones, we found that themicroarray data as shown in our Table 1 [2] are correct.However, in the text the column indicating the direction ofexpression “down or up” has been mistaken: “down” in thistable refers to a lower expression in anaplastic astrocytomas(AA) relative to glioblastomas (GBM).This is consistent with the other values given in the Table.The median expression levels for both groups were calcu-lated as mean log2-ratios. A negative result in the logarith-mic M AstroIII/GBM quotient represents an upregulation ofthe gene inGBM. In this regard the direction of the ex-pression level (FC) in column six can be misleading, butrepresents correctly the direction from GBM to AA and notvice versa, as we erroneously have used in the discussion [2].Unfortunately, the real-time PCR results in the same(small) group of tumors did in fact falsely indorse themisinterpreted results. Recent further investigation in alarger group of tumors (34 samples) of the same histologyhas meanwhile put into perspective the results of IL-13Rα2and Olig2. Olig2 had an almost 4-fold higher expression inAA (0,1146) compared to GBM (0,0294) with statisticalsignificance (p=0,025). IL-13Rα2 showed now a near equalexpression (AA 2,5078, GBM 2,7831) with no statisticalsignificance. Previous results [1, 5] showed significantdecline of gene expression with tumor grade and lowestexpression of Olig2 in GBM, which is now consistent withour further analysis and correctly interpreted array results.The equal expression of IL-13Rα2 in our recent larger PCRseries does not answer satisfactorily the question ofexpression differences between AA and GBM.These differences in real-time PCR quantification com-pared to the array results make their confirmation insecure.In similar studies Hoelzinger et al. confirmed only 19 genesout of 21 by quantitative RT-PCR [3] and van den Boomet al. in 9 out of 12 cases [6]. According to VandesompeleNeurosurg Rev (2008) 31:247–248DOI 10.1007/s10143-008-0125-9The online version of the original article can be found at http://dx.doi.org/10.1007/s10143-007-0107-3.O. Bozinov (*) :H. BertalanffyDepartment of Neurosurgery, University Hospital Zurich,Frauenklinikstrasse 10,8091 Zurich, Switzerlande-mail: oliver.bozinov@usz.chS. Köhler : L. Benes :D. Miller :U. SureDepartment of Neurosurgery,Philipps University Hospital Marburg,Marburg, GermanyB. SamansInstitute of Molecular Biology and Tumor Research,Philipps University Marburg,Marburg, GermanyM. RitterDepartment of Oncology, Sindelfingen Hospital,Sindelfingen, Germanyet al. normalization of real-time quantitative RT-PCR databy geometric averaging of multiple internal control genesmight be the solution and could open the possibility ofstudying the biological relevance of small expressiondifferences [7]. However, small series, such as ours, seamto be at risk for false confirmation and even further studiesin larger groups can be misleading. Additional tissue basedinvestigation, such as immunohistochemistry or in situhybridization may in future be more valuable to support theresults from the PCR studiesIt will be our obligation for the future, to provide profounddata on a large amount of tissue samples and differentquantification methods to clarify these uncertainties andinitial microarray analysis, especially regarding IL-13Rα2,which plays a critical biologic role in IL-13 cytotoxin-mediated therapy for GBM [4]. Any possible beneficial roleof this treatment regimen for GBM rather than for AAneeds to be confirmed by a larger series. Accordingly,clinical trials addressing the prognostic relevance mayhighlight the functional significance. The conclusion ofour article regarding the powerful approach of geneexpression profiling to identify transcriptional differencesof significance in gliomas remains [2], but its confirmationseems challenging and needs expansion to multiple quan-tification methods in order to avoid interpretation mistakes.References1. Bouvier C, Bartoli C, Guirre-Cruz L, Virard I, Colin C, Fernandez C etal (2003) Shared oligodendrocyte lineage gene expression in gliomasand oligodendrocyte progenitor cells. J Neurosurg 99:344–3502. Bozinov O, Köhler S, Samans B, Benes L, Miller D, Ritter M, SureU, Bertalanffy H (2008) Candidate genes for the progression ofmalignant gliomas identified by microarray analysis. NeurosurgRev 31:83–903. Hoelzinger DB, Mariani L, Weis J, Woyke T, Berens TJ,McDonough WS et al (2005) Gene expression profile ofglioblastoma multiforme invasive phenotype points to new thera-peutic targets. Neoplasia 7:7–164. Kawakami K, Kawakami K, Taguchi J, Murata T, Puri RK (2005)Evidence that IL-13R alpha2 chain in human glioma cells isresponsible for the antitumour activity mediated by receptor-directed cytotoxin therapy. J Immunother 28:193–2025. Mokhtari K, Paris S, Guirre-Cruz L, Privat N, Criniere E, Marie Yet al (2005) Olig2 expression, GFAP, p53 and 1p loss analysiscontribute to glioma subclassification. Neuropathol Appl Neurobiol31:62–696. van den Boom J, Wolter M, Kuick R, Misek DE, Youkilis AS,Wechsler DS et al (2003) Characterization of gene expressionprofiles associated with glioma progression using oligonucleotide-based microarray analysis and real-time reverse transcription-polymerase chain reaction. Am J Pathol 163:1033–10437. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, DePaepe A et al (2002) Accurate normalization of real-timequantitative RT-PCR data by geometric averaging of multipleinternal control genes. Genome Biol 18;3:RESEARCH0034248 Neurosurg Rev (2008) 31:247–248

Candidate genes for the progression of malignant gliomas identified by microarray analysis: Negative results in the logarithmic M AstroIII/GBM quotient represents upregulation of the gene

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Candidate genes for the progression of malignant gliomas identified by microarray analysis: Negative results in the logarithmic M AstroIII/GBM quotient represents upregulation of the gene

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