BRAFV600E Mutation in Gliomas in Iraqi Patients Immunohistochemical Study
International Journal of Clinical Oncology and Cancer Research
Volume 2, Issue 6, December 2017, Pages: 123-128
Received: Oct. 11, 2017; Accepted: Oct. 27, 2017; Published: Dec. 3, 2017
Views 1493      Downloads 80
Authors
Zahraa Marwan Shaban, Pathology Department and Forensic Medicine, College of Medicine, University of Mosul, Mosul, Iraq
Salim Rashid Al-Aubaidy, Pathology Department and Forensic Medicine, College of Medicine, University of Baghdad, Baghdad, Iraq
Article Tools
Follow on us
Abstract
Gliomas considered the most common primary malignant brain tumors in adults. BRAFV600E mutation occurs more in pediatric gliomas but less frequent in adult gliomas. This study aims to assess the frequency of BRAF mutation in Iraqi patients with gliomas by immunohistochemical study and to correlate its immunoreactivity with some clinicopathological parameters This work did on formalin fixed, paraffin embedded tumor tissue took from 66 patients with different grades of intracranial gliomas of both gender and all age groups in the Baghdad city. Ten normal brain tissue samples in form of paraffin blocks took from forensic medicine unit. New technique used, that was manual tissue microarray, in which twenty-four small cores (each measure 2mm) of represented tissue make, and then cut by microtome. Immunohistochemical detection of BRAFV600E antibody did by Dako autostainer link 48. BRAFV600E expressed as cytoplasmic staining in seven (10.60%) cases of glioma. It detected in pleomorphic xanthastrocytoma, oligodendroglioma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma and primary glioblastoma (100%, 9.1% 8.6%, 20.0%, 25% and 6.7%). It had a strong association with pediatric gliomas. From the work concluded that BRAFV600E mutation occurred in low percentage in gliomas especially adult types and significantly express in pediatric gliomas and some rare glial tumors.
Keywords
BRAF, Adults, Pediatric, Manual Tissue Microarray, Glioma, Immunohistochemical Study
To cite this article
Zahraa Marwan Shaban, Salim Rashid Al-Aubaidy, BRAFV600E Mutation in Gliomas in Iraqi Patients Immunohistochemical Study, International Journal of Clinical Oncology and Cancer Research. Vol. 2, No. 6, 2017, pp. 123-128. doi: 10.11648/j.ijcocr.20170206.11
Copyright
Copyright © 2017 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
References
[1]
Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M. Epidemiology and molecular pathology of glioma. Nature Clinical Practice Neurology. 2006; 2 (9):494-503.
[2]
Crocetti E, Trama A, Stiller C, et al. Epidemiology of glial and non-glial brain tumours in Europe. Eur J Cancer. 2012;48(10):1532–1542.
[3]
Emily A. J. Sehmer, G. J. Hall, David C. Greenberg, Catherine O’Hara, Sarah C. Wallingford, Karen A. Wright, et al. Incidence of glioma in a northwestern region of England, 2006–2010. Neuro-Oncology. 2014;16: 971–974.
[4]
Louis DN, Perry A, Reifenberger G, Deimling AV, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016; 131:803–820.
[5]
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO Classi Wcation of Tumours of the Central Nervous System. Acta Neuropathol. 2007;114:97–109.
[6]
Nikiforova MN, Hamilton RL. Molecular Diagnostics of Gliomas. Arch Pathol Lab Med. 2011;135:558–568.
[7]
Xia L, Wu B, Fu Z, Feng F, Qiao E, Li Q, et al. Prognostic role of IDH mutations in gliomas: a meta-analysis of 55 observational studies. Oncotarget 2015; 6 (19):17354-17365.
[8]
Jansen M, Yip S, Louis DN. Molecular pathology in adult neuro-oncology: an update on diagnostic, prognostic and predictive markers. Lancet Neurol. 2010; 9(7): 717–726.
[9]
El-Habr EA, Tsiorva P, Theodorou M, Levidou G, Korkolopoulou P, Vretakos G, et al. Analysis of PIK3CA and B-RAF gene mutations in human astrocytomas: association with activation of ERK and AKT. Clinical neuropathology 2010;6:24.
[10]
Ida CM, Vrana JA, Rodriguez FJ, Jentoft ME, Caron AA, Jenkins SM, et al. Immunohistochemistry is highly sensitive and specific for detection of BRAF V600E mutation in pleomorphic xanthoastrocytoma. Acta Neuropathologica Communications 2013, 1:20.
[11]
Gessi M, Pietsch T. The Diagnostic Role and Clinical Relevance of Determination of BRAF Status in Brain Tumors. Personalized medicine. 2013;10(4):405-412.
[12]
Flaherty KT, McArthur G. BRAF, a target in melanoma: implications for solid tumor drug development. Cancer. 2010;116(21):4902–4913.
[13]
Wan PT, Garnett MJ, Roe SM et al. Cancer Genome Project. Mechanism of activation of the RAF–ERK signaling pathway by oncogenic mutations of B-RAF. Cell. 2004;116, 855–867.
[14]
Davies H, Bignell GR, Cox C et al. Mutations of the BRAF gene in human cancer. Nature 2002;417:949–954.
[15]
Myung JK, Cho H, Park CK, Kim SK, Lee SH, Park SH: Analysis of the BRAF(V600E) Mutation in Central Nervous System Tumors. Transl Oncol 2012;5:430–436.
[16]
Dougherty MJ, Santi M, Brose MS et al. Activating mutations in BRAF characterize a spectrum of pediatric low-grade gliomas. Neuro. Oncol. 2010;12(7):621–630.
[17]
Schindler G, Capper D, Meyer J et al. Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol. 2011;121(3):397–405.
[18]
Forshew T, Tatevossian RG, Lawson AR, Ma J, Neale G, Ogunkolade BW, Jones TA, Aarum J, Dalton J, Bailey S, et al: Activation of the ERK/MAPK pathway: a signature genetic defect in posterior fossa pilocytic astrocytomas. J Pathol 2009; 218:172–181.
[19]
Lin A, Rodriguez FJ, Karajannis MA, Williams SC, Legault G, Zagzag D, Burger PC, Allen JC, Eberhart CG, Bar EE: BRAF alterations in primary glial and glioneuronal neoplasms of the central nervous system with identification of 2 novel KIAA1549:BRAF fusion variants. J Neuropathol Exp Neurol 2012; 71:66–72.
[20]
Rodriguez FJ, Ligon AH, Horkayne-Szakaly I, Rushing EJ, Ligon KL, Vena N, Garcia DI, Cameron JD, Eberhart CG: BRAF duplications and MAPK pathway activation are frequent in gliomas of the optic nerve proper. J Neuropathol Exp Neurol 2012; 71:789–794.
[21]
Dias-Santagata D, Lam Q, Vernovsky K, Vena N, Lennerz JK, Borger DR, Batchelor TT, Ligon KL, Iafrate AJ, Ligon AH, et al: BRAF V600E mutations are common in pleomorphic xanthoastrocytoma: diagnostic and therapeutic implications. PLoS One 2011;6:e17948.
[22]
Koelsche C, Wöhrer A, Jeibmann A et al. Mutant BRAF V600E protein in ganglioglioma is predominantly expressed by neuronal tumor cells. Acta Neuropathol. 2013; 13:1100-2.
[23]
Horbinski C. To BRAF or not to BRAF: is that even a question anymore? Neuropathol. Exp. Neurol. 2013;72(1):2–7.
[24]
Basto D, Trovisco V, Lopes JM et al. Mutation analysis of BRAF gene in human gliomas. Acta Neuropathol 2005;. 109(2):207–210.
[25]
http://www.3dhistech.com/TMA.
[26]
http://www.agilent.com/en/products/immunohistochemistry/
[27]
Schirosi L, Strippoli S, Gaudio F, Graziano G, Popescu O, Guida M, et al. Is immunohistochemistry of BRAF V600E useful as a screening tool and during progression disease of melanoma patients? BMC Cancer 2016;16:905.
[28]
Jeuken J, Broecke C, Gijsen S, Boots-Sprenger S, Wesseling P. RAS/RAF pathway activation in gliomas: the result of copy number gains rather than activating mutations. Acta Neuropathologica 2007;114 (2):121–133
[29]
Knobbe CB, Reifenberger J, and Reifenberger G. Mutation analysis of the Ras pathway genes NRAS, HRAS, KRAS and BRAF in glioblastomas. Acta Neuropathol 2004;108:467–470.
[30]
Behling F, Barrantes-Freer A, Skardelly M, Nieser M, Christians A, Stockhammer F, et al. Frequency of BRAF V600E mutations in 969 central nervous system neoplasms. Diagnostic Pathology 2016;11:55.
[31]
Hagemann C, Gloger J, Anacker J, Said HM, Gerngras S, Kuhnel S, Meyer C, Rapp UR, Kammerer U, Vordermark D, et al. (2009). RAF expression in human astrocytic tumors. Int J Mol Med 23, 17–31.
[32]
Schmidt Y, Kleinschmidt-Demasters BK, Aisner DL, Lillehei KO, Damek D. Anaplastic PXA in adults: case series with clinicopathologic and molecular features. J. Neurooncol. 2013;111(1), 59–69.
[33]
Gierke M, Sperveslage J, Schwab D, Beschorner R, Ebinger M, Schuhmann MU, et al. Analysis of IDH1-R132 mutation, BRAF V600 mutation and KIAA1549-BRAF fusion transcript status in central nervous system tumors supports pediatric tumor classification. J Cancer Res Clin Oncol. 2016;142(1):89–100.
[34]
Nicolaides TP, Li H, Solomon DA, Hariono S, Hashizume R, Barkovich K, et al. Targeted therapy for BRAF V600E malignant astrocytoma. Clin Cancer Res 2011;17:7595Y604.
ADDRESS
Science Publishing Group
1 Rockefeller Plaza,
10th and 11th Floors,
New York, NY 10020
U.S.A.
Tel: (001)347-983-5186