Diagnostic Utility of Immunohistochemical Detection of MEOX2, SOX11, INSM1 and EGFR in Gliomas
Status PubMed-not-MEDLINE Language English Country Switzerland Media electronic
Document type Journal Article
Grant support
NU20-03-00360
Ministry of Health
PubMed
37568909
PubMed Central
PMC10417822
DOI
10.3390/diagnostics13152546
PII: diagnostics13152546
Knihovny.cz E-resources
- Keywords
- CD34, EGFR, INSM1, MEOX2, SOX11, glioblastoma,
- Publication type
- Journal Article MeSH
Histological identification of dispersed glioma cells in small biopsies can be challenging, especially in tumours lacking the IDH1 R132H mutation or alterations in TP53. We postulated that immunohistochemical detection of proteins expressed preferentially in gliomas (EGFR, MEOX2, CD34) or during embryonal development (SOX11, INSM1) can be used to distinguish reactive gliosis from glioma. Tissue microarrays of 46 reactive glioses, 81 glioblastomas, 34 IDH1-mutant diffuse gliomas, and 23 gliomas of other types were analysed. Glial neoplasms were significantly more often (p < 0.001, χ2) positive for EGFR (34.1% vs. 0%), MEOX2 (49.3% vs. 2.3%), SOX11 (70.5% vs. 20.4%), and INSM1 (65.4% vs. 2.3%). In 94.3% (66/70) of the glioblastomas, the expression of at least two markers was observed, while no reactive gliosis showed coexpression of any of the proteins. Compared to IDH1-mutant tumours, glioblastomas showed significantly higher expression of EGFR, MEOX2, and CD34 and significantly lower positivity for SOX11. Non-diffuse gliomas were only rarely positive for any of the five markers tested. Our results indicate that immunohistochemical detection of EGFR, MEOX2, SOX11, and INSM1 can be useful for detection of glioblastoma cells in limited histological samples, especially when used in combination.
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Capper D., Sahm F., Hartmann C., Meyermann R., von Deimling A., Schittenhelm J. Application of Mutant IDH1 Antibody to Differentiate Diffuse Glioma From Nonneoplastic Central Nervous System Lesions and Therapy-induced Changes. Am. J. Surg. Pathol. 2010;34:1199–1204. doi: 10.1097/PAS.0b013e3181e7740d. PubMed DOI
Hartmann C., Meyer J., Balss J., Capper D., Mueller W., Christians A., Felsberg J., Wolter M., Mawrin C., Wick W., et al. Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oli-godendroglial differentiation and age: A study of 1010 diffuse gliomas. Acta Neuropathol. 2009;118:469–474. doi: 10.1007/s00401-009-0561-9. PubMed DOI
Balss J., Meyer J., Mueller W., Korshunov A., Hartmann C., von Deimling A. Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol. 2008;116:597–602. doi: 10.1007/s00401-008-0455-2. PubMed DOI
Parsons D.W., Jones S., Zhang X., Lin J.C.-H., Leary R.J., Angenendt P., Mankoo P., Carter H., Siu I.-M., Gallia G.L., et al. An integrated enomic analysis of human glioblastoma multiforme. Science. 2008;321:1807–1812. doi: 10.1126/science.1164382. PubMed DOI PMC
Verhaak R.G., Hoadley K.A., Purdom E., Wang V., Qi Y., Wilkerson M.D., Miller C.R., Ding L., Golub T., Mesirov J.P., et al. Integrated genomic analysis identifies clinically relevant subtypes of glio-blastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17:98–110. doi: 10.1016/j.ccr.2009.12.020. PubMed DOI PMC
Louis D.N., Perry A., Wesseling P., Brat D.J., Cree I.A., Figarella-Branger D., Hawkins C., Ng H.K., Pfister S.M., Reifenberger G., et al. The 2021 WHO Classification of Tumors of the Central Nervous System: A summary. Neuro-Oncology. 2021;23:1231–1251. doi: 10.1093/neuonc/noab106. PubMed DOI PMC
Tanboon J., Williams E.A., Louis D.N. The Diagnostic Use of Immunohistochemical Surrogates for Signature Molecular Genetic Alterations in Gliomas. J. Neuropathol. Exp. Neurol. 2015;75:4–18. doi: 10.1093/jnen/nlv009. PubMed DOI
Yaziji H., Massarani-Wafai R., Gujrati M., Kuhns J.G., Martin A.W., Parker J.C. Role of p53 Immunohistochemistry in Differentiating Reactive Gliosis From Malignant Astrocytic Lesions. Am. J. Surg. Pathol. 1996;20:1086–1090. doi: 10.1097/00000478-199609000-00006. PubMed DOI
Pastrana E., Cheng L.-C., Doetsch F. Simultaneous prospective purification of adult subventricular zone neural stem cells and their progeny. Proc. Natl. Acad. Sci. USA. 2009;106:6387–6392. doi: 10.1073/pnas.0810407106. PubMed DOI PMC
Eskilsson E., Røsland G.V., Solecki G., Wang Q., Harter P.N., Graziani G., Verhaak R.G.W., Winkler F., Bjerkvig R., Miletic H. EGFR heterogeneity and implications for therapeutic intervention in glioblastoma. Neuro-Oncology. 2017;20:743–752. doi: 10.1093/neuonc/nox191. PubMed DOI PMC
Tachon G., Masliantsev K., Rivet P., Petropoulos C., Godet J., Milin S., Wager M., Guichet P.-O., Karayan-Tapon L. Prognostic significance of MEOX2 in gliomas. Mod. Pathol. 2019;32:774–786. doi: 10.1038/s41379-018-0192-6. PubMed DOI
Tachon G., Masliantsev K., Rivet P., Desette A., Milin S., Gueret E., Wager M., Karayan-Tapon L., Guichet P.-O. MEOX2 Transcription Factor Is Involved in Survival and Adhesion of Glioma Stem-like Cells. Cancers. 2021;13:5943. doi: 10.3390/cancers13235943. PubMed DOI PMC
Duggan A., Madathany T., de Castro S.C., Gerrelli D., Guddati K., García-Añoveros J. Transient expression of the conserved zinc finger gene INSM1 in progenitors and nascent neurons throughout embryonic and adult neurogenesis. J. Comp. Neurol. 2008;507:1497–1520. doi: 10.1002/cne.21629. PubMed DOI
Wang Y., Lin L., Lai H., Parada L.F., Lei L. Transcription factor Sox11 is essential for both embryonic and adult neurogenesis. Dev. Dyn. 2013;242:638–653. doi: 10.1002/dvdy.23962. PubMed DOI
Haslinger A., Schwarz T.J., Covic M., Lie D.C. Expression of Sox11 in adult neurogenic niches suggests a stage-specific role in adult neurogenesis. Eur. J. Neurosci. 2009;29:2103–2114. doi: 10.1111/j.1460-9568.2009.06768.x. PubMed DOI
Ames H.M., Rooper L.M., Laterra J.J., Eberhart C.G., Rodriguez F.J. INSM1 Expression Is Frequent in Primary Central Nervous System Neoplasms but Not in the Adult Brain Parenchyma. J. Neuropathol. Exp. Neurol. 2018;77:374–382. doi: 10.1093/jnen/nly014. PubMed DOI PMC
Farkas L.M., Haffner C., Giger T., Khaitovich P., Nowick K., Birchmeier C., Pääbo S., Huttner W.B. Insulinoma-Associated 1 Has a Panneurogenic Role and Promotes the Generation and Expansion of Basal Progenitors in the Developing Mouse Neocortex. Neuron. 2008;60:40–55. doi: 10.1016/j.neuron.2008.09.020. PubMed DOI
Korkolopoulou P., Levidou G., El-Habr E.A., Adamopoulos C., Fragkou P., Boviatsis E., Themistocleous M.S., Petraki K., Vrettakos G., Sakalidou M., et al. Sox11 expression in astrocytic gliomas: Correlation with nes-tin/c-Met/IDH1-R132H expression phenotypes, p-Stat-3 and survival. Br. J. Cancer. 2013;108:2142–2152. doi: 10.1038/bjc.2013.176. PubMed DOI PMC
Xu S., Dong Y., Huo Z., Yu L., Xue J., Wang G., Duan Y. SOX11: A potentially useful marker in surgical pathology: A systematic analysis of SOX11 expression in epithelial and non-epithelial tumours. Histopathology. 2018;74:391–405. doi: 10.1111/his.13757. PubMed DOI
Hide T., Takezaki T., Nakatani Y., Nakamura H., Kuratsu J.I., Kondo T. Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differ-entiation. Cancer Res. 2009;69:7953–7959. doi: 10.1158/0008-5472.CAN-09-2006. PubMed DOI
Sidney L.E., Branch M.J., Dunphy S.E., Dua H.S., Hopkinson A. Concise Review: Evidence for CD34 as a Common Marker for Diverse Progenitors. Stem Cells. 2014;32:1380–1389. doi: 10.1002/stem.1661. PubMed DOI PMC
Blümcke I., Giencke K., Wardelmann E., Beyenburg S., Kral T., Sarioglu N., Pietsch T., Wolf H.K., Schramm J., Elger C.E., et al. The CD34 epitope is expressed in neoplastic and malformative lesions associated with chronic, focal epilepsies. Acta Neuropathol. 1999;97:481–490. doi: 10.1007/s004010051017. PubMed DOI
Giulioni M., Marucci G., Cossu M., Tassi L., Bramerio M., Barba C., Buccoliero A.M., Vornetti G., Zenesini C., Consales A., et al. CD34 Expression in Low-Grade Epilepsy-Associated Tumors: Relationships with Clinicopathologic Features. World Neurosurg. 2018;121:e761–e768. doi: 10.1016/j.wneu.2018.09.212. PubMed DOI
Burel-Vandenbos F., Benchetrit M., Miquel C., Fontaine D., Auvergne R., Lebrun-Frenay C., Cardot-Leccia N., Michiels J.-F., Paquis-Flucklinger V., Virolle T. EGFR immunolabeling pattern may discriminate low-grade gliomas from gliosis. J. Neuro-Oncol. 2010;102:171–178. doi: 10.1007/s11060-010-0308-4. PubMed DOI
Conroy S., Kruyt F.A.E., Joseph J.V., Balasubramaniyan V., Bhat K.P., Wagemakers M., Enting R.H., Walenkamp A.M.E., Dunnen W.F.A.D. Subclassification of Newly Diagnosed Glioblastomas through an Immunohistochemical Approach. PLoS ONE. 2014;9:e115687. doi: 10.1371/journal.pone.0115687. PubMed DOI PMC
Guillaudeau A., Durand K., Pommepuy I., Robert S., Chaunavel A., Lacorre S., DeArmas R., Bourtoumieux S., El Demery M., Moreau J.-J., et al. Determination of EGFR status in gliomas: Usefulness of immunohistochem-istry and fluorescent in situ hybridization. Appl. Immunohistochem. Mol. Morphol. 2009;17:220–226. doi: 10.1097/PAI.0b013e31818db320. PubMed DOI
Popova S.N., Bergqvist M., Dimberg A., Edqvist P.-H., Ekman S., Hesselager G., Ponten F., Smits A., Sooman L., Alafuzoff I. Subtyping of gliomas of various WHO grades by the application of immuno-histochemistry. Histopathology. 2014;64:365–379. doi: 10.1111/his.12252. PubMed DOI PMC
Yang Z., Jiang S., Lu C., Ji T., Yang W., Li T., Lv J., Hu W., Yang Y., Jin Z. SOX11: Friend or foe in tumor prevention and carcinogenesis? Ther. Adv. Med. Oncol. 2019;11:1758835919853449. doi: 10.1177/1758835919853449. PubMed DOI PMC
Lan M.S., Breslin M.B. Structure, expression, and biological function of INSM1 transcription factor in neuroendocrine differentiation. FASEB J. 2009;23:2024–2033. doi: 10.1096/fj.08-125971. PubMed DOI PMC
Bao Z.S., Zhang C.B., Wang H.J., Yan W., Liu Y.W., Li M.Y., Zhang W. Whole-genome mRNA expression profiling identifies functional and prognostic sig-natures in patients with mesenchymal glioblastoma multiforme. CNS Neurosci. Ther. 2013;19:714–720. doi: 10.1111/cns.12118. PubMed DOI PMC
Lohkamp L.-N., Schinz M., Gehlhaar C., Guse K., Thomale U.-W., Vajkoczy P., Heppner F.L., Koch A. MGMT Promoter Methylation and BRAF V600E Mutations Are Helpful Markers to Discriminate Pleomorphic Xanthoastrocytoma from Giant Cell Glioblastoma. PLoS ONE. 2016;11:e0156422. doi: 10.1371/journal.pone.0156422. PubMed DOI PMC
Galloway M. CD34 expression in glioblastoma and giant cell glioblastoma. Clin. Neuropathol. 2010;29:89–93. doi: 10.5414/NPP29089. PubMed DOI
Burel-Vandenbos F., Turchi L., Benchetrit M., Fontas E., Pedeutour Z., Rigau V., Almairac F., Ambrosetti D., Michiels J.-F., Virolle T. Cells with intense EGFR staining and a high nuclear to cytoplasmic ratio are specific for infiltrative glioma: A useful marker in neuropathological practice. Neuro-Oncology. 2013;15:1278–1288. doi: 10.1093/neuonc/not094. PubMed DOI PMC
Hölzl D., Hutarew G., Zellinger B., Alinger-Scharinger B., Schlicker H.U., Schwartz C., Sotlar K., Kraus T.F.J. EGFR Amplification Is a Phenomenon of IDH Wildtype and TERT Mutated High-Grade Glioma: An Integrated Analysis Using Fluorescence In Situ Hybridization and DNA Methylome Profiling. Biomedicines. 2022;10:794. doi: 10.3390/biomedicines10040794. PubMed DOI PMC
Li K.K.-W., Shi Z.-F., Malta T.M., Chan A.K.-Y., Cheng S., Kwan J.S.H., Yang R.R., Poon W.S., Mao Y., Noushmehr H., et al. Identification of subsets of IDH-mutant glioblastomas with distinct epigenetic and copy number alterations and stratified clinical risks. Neuro-Oncol. Adv. 2019;1 doi: 10.1093/noajnl/vdz015. PubMed DOI PMC
Uhlén M., Fagerberg L., Hallström B.M., Lindskog C., Oksvold P., Mardinoglu A., Sivertsson Å., Kampf C., Sjöstedt E., Asplund A., et al. Proteomics. Tissue-Based Map of the Human Proteome. Science. 2015;347:1260419. doi: 10.1126/science.1260419. PubMed DOI
Sharain R.F., Gown A.M., Greipp P.T., Folpe A.L. Immunohistochemistry for TFE3 lacks specificity and sensitivity in the diagnosis of TFE3-rearranged neoplasms: A comparative, 2-laboratory study. Hum. Pathol. 2019;87:65–74. doi: 10.1016/j.humpath.2019.02.008. PubMed DOI
Teo W.-Y., Sekar K., Seshachalam P., Shen J., Chow W.-Y., Lau C.C., Yang H., Park J., Kang S.-G., Li X., et al. Relevance of a TCGA-derived Glioblastoma Subtype Gene-Classifier among Patient Populations. Sci. Rep. 2019;9:7442. doi: 10.1038/s41598-019-43173-y. PubMed DOI PMC
Swiss V.A., Nguyen T., Dugas J., Ibrahim A., Barres B., Androulakis I.P., Casaccia P. Identification of a gene regulatory network necessary for the initiation of oligoden-drocyte differentiation. PLoS ONE. 2011;6:e18088. doi: 10.1371/journal.pone.0018088. PubMed DOI PMC
Camacho-Urkaray E., Santos-Juanes J., Gutiérrez-Corres F.B., García B., Quirós L.M., Guerra-Merino I., Aguirre J.J., Fernández-Vega I. Establishing cut-off points with clinical relevance for bcl-2, cyclin D1, p16, p21, p27, p53, Sox11 and WT1 expression in glioblastoma - a short report. Cell. Oncol. 2017;41:213–221. doi: 10.1007/s13402-017-0362-4. PubMed DOI
Guan X., Vengoechea J., Zheng S., Sloan A.E., Chen Y., Brat D.J., O’neill B.P., de Groot J., Yust-Katz S., Yung W.-K.A., et al. Molecular Subtypes of Glioblastoma Are Relevant to Lower Grade Glioma. PLoS ONE. 2014;9:e91216. doi: 10.1371/journal.pone.0091216. PubMed DOI PMC
Motomura K., Natsume A., Watanabe R., Ito I., Kato Y., Momota H., Nishikawa R., Mishima K., Nakasu Y., Abe T., et al. Immunohistochemical analysis-based proteomic subclassification of newly diagnosed glioblastomas. Cancer Sci. 2012;103:1871–1879. doi: 10.1111/j.1349-7006.2012.02377.x. PubMed DOI PMC
McTigue D.M., Tripathi R.B. The life, death, and replacement of oligodendrocytes in the adult CNS. J. Neurochem. 2008;107:1–19. doi: 10.1111/j.1471-4159.2008.05570.x. PubMed DOI
Lu I.-N., Dobersalske C., Rauschenbach L., Teuber-Hanselmann S., Steinbach A., Ullrich V., Prasad S., Blau T., Kebir S., Siveke J.T., et al. Tumor-associated hematopoietic stem and progenitor cells positively linked to glioblastoma progression. Nat. Commun. 2021;12:1–16. doi: 10.1038/s41467-021-23995-z. PubMed DOI PMC
Kovacs M., Trias E., Varela V., Ibarburu S., Beckman J.S., Moura I.C., Hermine O., King P.H., Si Y., Kwon Y., et al. CD34 Identifies a Subset of Proliferating Microglial Cells Associated with Degenerating Motor Neurons in ALS. Int. J. Mol. Sci. 2019;20:3880. doi: 10.3390/ijms20163880. PubMed DOI PMC
Soldini D., Valera A., Solé C., Palomero J., Amador V., Martin-Subero J.I., Ribera-Cortada I., Royo C., Salaverria I., Beà S., et al. Assessment of SOX11 expression in routine lymphoma tissue sections: Characterization of new monoclonal antibodies for diagnosis of mantle cell lymphoma. Am. J. Surg. Pathol. 2014;38:86–93. doi: 10.1097/PAS.0b013e3182a43996. PubMed DOI
Torlakovic E.E., Nielsen S., Vyberg M., Taylor C.R. Getting controls under control: The time is now for immunohistochemistry. J. Clin. Pathol. 2015;68:879–882. doi: 10.1136/jclinpath-2014-202705. PubMed DOI PMC
Expression of STAT3 and hypoxia markers in long-term surviving malignant glioma patients