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Cytokeratin AE1/AE3 mimicry in glioblastoma

George St. Stoyanov, Deyan Dzhenkov, Peter Ghenev

Abstract

INTRODUCTION: The diagnosis and treatment of intracranial tumors requires a multidisciplinary approach. A key moment in this process is the pathological verification of the tumor type. This process, although aided by immunohistochemistry (IHC), can often be difficult and misleading.

MATERIALS AND METHODS: Ten histologically confirmed cases of glioblastoma multiforme (GBM) were reviewed for their IHC reaction with the anti-glial fibrillary acidic protein (GFAP) glial marker and the CK AE1/AE3 antibody cocktail, whose main use in neuropathology is to either prove or rule out metastatic cancer of epithelial origin, the primary location of which may not be known or even suspected.

RESULTS: All ten pathologically verified cases of GBM were diagnostically positive for GFAP, with eight of them also revealing CK AE1/AE3 expression with variable intensity. Out of the CK AE1/AE3 positive cases, five (50% in total) gave a low to intermediate non-diagnostic positive reaction, while the other three cases (30% in total) gave a strong positive reaction with possible diagnostic value. Cells, across all GBM cases, that tested positive for CK AE1/AE3, regardless of the strength of the reaction, were also positive for GFAP on neighboring IHC serial slides.

CONCLUSION: The presented results reveal CK AE1/AE3 expression in a great portion of GBM cases, which may be caused by three-dimensional mimicry between the CK AE1/AE3 and GFAP target molecules. This therefore necessitates the need for a careful interpretation of the results. CK AE1/AE3, however, remains a useful tool in neuropathology, regardless of the possibility of false positivity in GBM cells.


Keywords

glioblastoma, IHC, CNS tumor, antigene mimcry

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References

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007;114(2):97-109.

Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, Stroup NE, Kruchko C, Barnholtz- Sloan JS. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro Oncol 2013;15 Suppl 2:1-56.

Gavrilovic IT, Posner JB Brain Metastases: Epidemiology and Pathophysiology. J Neuro Oncol 2005;75: 5-14. doi: 10.1007/s11060-004-8093-6

Walker AE, Robins M, Weinfeld FD Epidemiology of Brain Tumors the National Survey of Intracranial Neoplasms. Neurol 1985;35:219-219. doi: 10.1212/WNL.35.2.219

Fogelholm R, Uutela T, Murros K. Epidemiology of central nervous system neoplasms. A regional survey in Central Finland. Acta Neurol Scand 1984;69(3):129-36.

Krex D, Klink B, Hartmann C, von Deimling A, Pietsch T, Simon M, Sabel M, Steinbach JP, Heese O, Reifenberger G, Weller M, Schackert G Long term survival with glioblastoma multiforme. Brain 2007;130:2569-606. doi: http://dx.doi.org/10.1093/brain/awm204

Coons SW, Johnson PC, Scheithauer BW, Yates AJ, Pearl DK Improving diagnostic accuracy and interobserver concordance in the classification and grading of primary gliomas. Cancer 1997;79:1381-93. doi: 10.1002/(SICI)1097- 0142(19970401)79:7<1381::AID-CNCR16>3.0.CO;2- W

Gravendeel LA, Kouwenhoven MC, Gevaert O, de Rooi JJ, Stubbs AP, Duijm JE, Daemen A, Bleeker FE, Bralten LB, Kloosterhof NK, De Moor B, Eilers PH, van der Spek PJ, Kros JM, Sillevis Smitt PA, van den Bent MJ, French PJ Intrinsic gene expression profiles of gliomas are a better predictor of survival than histology. Cancer res 2009;69:9065- 72. doi: 10.1158/0008-5472.CAN-09-2307

Popova SN, Bergqvist M, Dimberg A, Edqvist PH, Ekman S, Hesselager G, Ponten F, Smits A, Sooman L, Alafuzoff I Subtyping of gliomas of various WHO grades by the application of immunohistochemistry. Histopathology 2014;64:365-79. doi: 10.1111/his.12252

Oh D, Prayson RA Evaluation of epithelial and keratin markers in glioblastoma multiforme: an immunohistochemical study. Arch Pathol Lab Med 1999;123(10):917-20

Stoyanov G, Dzhenkov D, Ghenev P. The Great Imitator - EMA positive glioblastoma multiforme. Scri Sci Med 2017;49(1):online first. doi: 10.14748/ssm.v49i1.2056

Kriho VK, Yang HY, Moskal JR, Skalli O. Keratin expression in astrocytomas: an immunofluorescent and biochemical reassessment. Virchows Arch 1997;431(2):139-47.

Goswami C, Chatterjee U, Sen S, Chatterjee S, Sarkar S. Expression of cytokeratins in gliomas. Indian J Pathol Microbiol 2007;50(3):478-81.

Cosgrove MM, Rich KA, Kunin SA, Sherrod AE, Martin SE. Keratin intermediate filament expression in astrocytic neoplasms: analysis by immunocytochemistry, western blot, and northern hybridization. Mod Pathol 1993;6(3):342-7.

Terada T Expression of cytokeratins in glioblastoma multiforme. Pathol Oncol Res 2015;21:817-9. doi: 10.1007/s12253-015-9896-9

Dako Monoclonal mouse anti-human Cytokeratin AE1/AE3. http://www.dako.com/dist/ar38/p103580/prod_products.htm

Dako Polyclonal rabbit anti-GFAP. http://www.dako.com/dist/ar49/p235483/prod_products.htm

Olar A, Aldape KD Using the molecular classification of glioblastoma to inform personalized treatment. J Pathol 2014;232:165-77. doi: 10.1002/path.4282

Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O`Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, Perou CM, Hayes DN. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010;17(1):98-110

Crespo I, Vital AL, Gonzalez-Tablas M, Patino Mdel C, Otero A, Lopes MC, de Oliveira C, Domingues P, Orfao A, Tabernero MD Molecular and Genomic Alterations in Glioblastoma Multiforme. Am J Pathol 2015;185:1820-33. doi: 10.1016/j. ajpath.2015.02.023

Antoch G, Vogt FM, Freudenberg LS, Nazaradeh F, Goehde SC, Barkhausen J, Dahmen G, Bockisch A, Debatin JF, Ruehm SG Whole-body dual-modality PET/CT and whole-body MRI for tumor staging in oncology. JAMA 2003;290:3199-206. doi: 10.1001/ jama.290.24.3199




DOI: http://dx.doi.org/10.14748/ssm.v49i1.2055
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About The Authors

George St. Stoyanov
Medical University of Varna
Bulgaria

Department of General and Clinical Pathology, Forensic Medicine and Deontology

Deyan Dzhenkov
Medical University of Varna
Bulgaria

Department of General and Clinical Pathology, Forensic Medicine and Deontology

Peter Ghenev
Medical University of Varna

Department of General and Clinical Pathology, Forensic Medicine and Deontology

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